Journal of Mammary Gland Biology and Neoplasia, 2009
That milk secretion is not the final differentiated state of the mammary alveolar cells is a rela... more That milk secretion is not the final differentiated state of the mammary alveolar cells is a relatively new concept. Recent work has suggested that secreting, mammary epithelial cells (MECs) have another function to perform before they undergo cell death in the involuting mammary gland. That is, they help in the final clearance and breakdown of their neighboring cells (and likely residual milk as well.) They become, for a short time, amateur phagocytes, or efferocytes, and then are believed to die and be cleared themselves. Although relatively little study has been made of this change in the functional state of the MEC, nevertheless we may speculate from the involution literature, and extend findings from other systems of apoptotic cell clearance, on some of the mechanisms involved. And with the finding that involution may represent a unique susceptibility window for the progression of metastatic breast cancer, we may suggest areas for future research along these lines as well.
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism
... of 5-1ipoxygenase products in platelet-neutrophil co-incubations Catherine Antoine ~,.h Rober... more ... of 5-1ipoxygenase products in platelet-neutrophil co-incubations Catherine Antoine ~,.h Robert C. Murphy ~', Peter M. Henson ~' and Jacques Maclouf b " National Jewixh ('enter fiw hnmuntdo,~' aml RespiratoD' Medicine. Dent r('Jr, ("0 t USA ) and ~" Unitt: 348 INSERM, Ih;pital ...
American journal of respiratory cell and molecular biology, Jul 3, 2017
The current paradigm in macrophage biology is that some tissues mainly contain macrophages from e... more The current paradigm in macrophage biology is that some tissues mainly contain macrophages from embryonic origin such as microglia in the brain, while other tissues contain postnatal-derived macrophages, such as the gut. However, in the lung and in other organs such as the skin, there are both embryonic and postnatal-derived macrophages. In this study, we demonstrate in the steady-state lung that the mononuclear phagocyte system is comprised of three newly identified interstitial macrophages (IMs), alveolar macrophages (AMs), dendritic cells (DCs) and few extravascular monocytes. We focused on similarities and differences between the three IM subtypes, specifically, their phenotype, location, transcriptional signature, phagocytic capacity, turnover and lack of survival dependency on CX3CR1. Pulmonary IMs were located in the bronchial interstitium but not the alveolar interstitium. At the transcriptional level, all three IMs displayed a macrophage signature and phenotype. All IMs exp...
Circulating 51Cr-labeled platelets accumulate at skin sites in which a reversed passive Arthus re... more Circulating 51Cr-labeled platelets accumulate at skin sites in which a reversed passive Arthus reaction has been induced. The accumulation is biphasic in time and is accompanied by an increased vascular permeability. Increased permeability itself, however, will not produce localization of platelets. A similar platelet accumulation was observed upon injection of compound 48/80 or anti-IgE antibody into the skin and this was not altered in rabbits depleted of complement or neutrophils. Activation of skin mast cells and release of a platelet-activating factor (PAF) is suggested as a mechanism for the effect produced by anti-IgE and compound 48/80. The first phase of platelet accumulation in the Arthus reaction was also unaffected in rabbits depleted of neutrophils or complement, which may suggest a role for IgE antibody and mast cells. The second phase of accumulation was diminished in complement-depleted animals and abrogated in rabbits without neutrophils, suggesting a complement and neutrophil-mediated process but which still might be mediated through mast cell activation by neutrophil cationic protein.
Human neutrophils released the granule constituents myeloperoxidase and lysozyme, but not the cyt... more Human neutrophils released the granule constituents myeloperoxidase and lysozyme, but not the cytoplasmic enzyme lactic dehydrogenase, when pretreated with cytochalasin B and stimulated with purified human C5a. Prior exposure to C5a before the cytochalasin B, however, abrogated the subsequent secretory process. Interaction of neutrophils with C5a was shown to result in a concentration-dependent rapid desensitization that could not be overcome by later addition of cytochalasin B or of cytochalasin B and C5a. The effect was relatively stimulus specific in that neutrophils desensitized in this manner could be induced to release granule enzymes by casein or by complement-coated zymosan particles. Cytochalasin B effects on neutrophils appear to mimic those of surface binding of soluble stimuli such as C5a and immune complexes. It is suggested that desensitization in concert with surface stimulation may represent an important intracellular mechanism for limiting neutrophil secretion.
MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase that, in ... more MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase that, in addition to regulating the c-Jun NH(2)-terminal kinase (JNK) pathway, is involved in the control of cell motility. MEKK1(-/-) mice are defective in eyelid closure, a TGFalpha-directed process involving the migration of epithelial cells. MEKK1 expression in epithelial cells stimulates lamellipodia formation, a process required for cell movement. In addition, mouse embryo fibroblasts derived from MEKK1(-/-) mice are inhibited in their migration relative to MEKK1(+/+) fibroblasts. MEKK1 is required for JNK but not NF-kappaB activation in response to virus infection, microtubule disruption, and stimulation of embryonic stem cells with lysophosphatidic acid. MEKK1 is not required for TNFalpha or IL-1 regulation of JNK or NF-kappaB activation in macrophages or fibroblasts. Thus, MEKK1 senses microtubule integrity, contributes to the regulation of fibroblast and epithelial cell migration, and is required for activation of JNK but not NF-kappaB in response to selected stress stimuli.
Two types of highly purified, structurally defined LPS molecules prepared from Escherichia coli 0... more Two types of highly purified, structurally defined LPS molecules prepared from Escherichia coli 0111:B4 and Salmonella minnesota Re595 have been shown to differ significantly in their capacity to activate serum complement. However, both preparations, when injected i.v. into normal rabbits, rabbits depleted of C3, or rabbits genetically deficient in C6 produced almost identical decreases in blood pressure over a 5-hr period (post-injection). These changes were characterized by an initial decrease (20 to 30%) in blood pressure 30 to 60 min post-injection followed by a secondary fall in pressure beginning 120 min post-injection. No decreases in either C3 levels (radial immunodiffusion) or CH 50 values were detected after injection of either LPS preparation. The data suggests that the participation of C3 and the terminal complement components are not essential for LPS-induced hypotension. Additional support for this conclusion derives from experiments designed to examine directly the effect of complement activation in vivo on blood pressure.
Human and rabbit peripheral blood monocytes normally adhere to plastic tissue culture plates in v... more Human and rabbit peripheral blood monocytes normally adhere to plastic tissue culture plates in vitro when they are suspended in Hanks' media. Increasing amounts of autologous serum or heat-inactivated plasma in the cell suspensions prevented the adherence of both monocytes and lymphocytes. The inhibitory effect of plasma was separated into three areas of activity by chromatography on Sephacryl S-200. The profile of inhibitory activity did not coincide with the protein elution profile, suggesting that inhibition was not a nonspecific protein effect. A layer of adherent platelets overcame the inhibitory effect of plasma on monocyte adherence. Platelets selectively increased monocyte as opposed to lymphocyte adherence and this was specific for platelets in that neither neutrophils nor fibroblasts could substitute for platelets. Both plasma and platelets acted directly on monocytes.
Journal of Mammary Gland Biology and Neoplasia, 2009
That milk secretion is not the final differentiated state of the mammary alveolar cells is a rela... more That milk secretion is not the final differentiated state of the mammary alveolar cells is a relatively new concept. Recent work has suggested that secreting, mammary epithelial cells (MECs) have another function to perform before they undergo cell death in the involuting mammary gland. That is, they help in the final clearance and breakdown of their neighboring cells (and likely residual milk as well.) They become, for a short time, amateur phagocytes, or efferocytes, and then are believed to die and be cleared themselves. Although relatively little study has been made of this change in the functional state of the MEC, nevertheless we may speculate from the involution literature, and extend findings from other systems of apoptotic cell clearance, on some of the mechanisms involved. And with the finding that involution may represent a unique susceptibility window for the progression of metastatic breast cancer, we may suggest areas for future research along these lines as well.
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism
... of 5-1ipoxygenase products in platelet-neutrophil co-incubations Catherine Antoine ~,.h Rober... more ... of 5-1ipoxygenase products in platelet-neutrophil co-incubations Catherine Antoine ~,.h Robert C. Murphy ~', Peter M. Henson ~' and Jacques Maclouf b " National Jewixh ('enter fiw hnmuntdo,~' aml RespiratoD' Medicine. Dent r('Jr, ("0 t USA ) and ~" Unitt: 348 INSERM, Ih;pital ...
American journal of respiratory cell and molecular biology, Jul 3, 2017
The current paradigm in macrophage biology is that some tissues mainly contain macrophages from e... more The current paradigm in macrophage biology is that some tissues mainly contain macrophages from embryonic origin such as microglia in the brain, while other tissues contain postnatal-derived macrophages, such as the gut. However, in the lung and in other organs such as the skin, there are both embryonic and postnatal-derived macrophages. In this study, we demonstrate in the steady-state lung that the mononuclear phagocyte system is comprised of three newly identified interstitial macrophages (IMs), alveolar macrophages (AMs), dendritic cells (DCs) and few extravascular monocytes. We focused on similarities and differences between the three IM subtypes, specifically, their phenotype, location, transcriptional signature, phagocytic capacity, turnover and lack of survival dependency on CX3CR1. Pulmonary IMs were located in the bronchial interstitium but not the alveolar interstitium. At the transcriptional level, all three IMs displayed a macrophage signature and phenotype. All IMs exp...
Circulating 51Cr-labeled platelets accumulate at skin sites in which a reversed passive Arthus re... more Circulating 51Cr-labeled platelets accumulate at skin sites in which a reversed passive Arthus reaction has been induced. The accumulation is biphasic in time and is accompanied by an increased vascular permeability. Increased permeability itself, however, will not produce localization of platelets. A similar platelet accumulation was observed upon injection of compound 48/80 or anti-IgE antibody into the skin and this was not altered in rabbits depleted of complement or neutrophils. Activation of skin mast cells and release of a platelet-activating factor (PAF) is suggested as a mechanism for the effect produced by anti-IgE and compound 48/80. The first phase of platelet accumulation in the Arthus reaction was also unaffected in rabbits depleted of neutrophils or complement, which may suggest a role for IgE antibody and mast cells. The second phase of accumulation was diminished in complement-depleted animals and abrogated in rabbits without neutrophils, suggesting a complement and neutrophil-mediated process but which still might be mediated through mast cell activation by neutrophil cationic protein.
Human neutrophils released the granule constituents myeloperoxidase and lysozyme, but not the cyt... more Human neutrophils released the granule constituents myeloperoxidase and lysozyme, but not the cytoplasmic enzyme lactic dehydrogenase, when pretreated with cytochalasin B and stimulated with purified human C5a. Prior exposure to C5a before the cytochalasin B, however, abrogated the subsequent secretory process. Interaction of neutrophils with C5a was shown to result in a concentration-dependent rapid desensitization that could not be overcome by later addition of cytochalasin B or of cytochalasin B and C5a. The effect was relatively stimulus specific in that neutrophils desensitized in this manner could be induced to release granule enzymes by casein or by complement-coated zymosan particles. Cytochalasin B effects on neutrophils appear to mimic those of surface binding of soluble stimuli such as C5a and immune complexes. It is suggested that desensitization in concert with surface stimulation may represent an important intracellular mechanism for limiting neutrophil secretion.
MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase that, in ... more MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase that, in addition to regulating the c-Jun NH(2)-terminal kinase (JNK) pathway, is involved in the control of cell motility. MEKK1(-/-) mice are defective in eyelid closure, a TGFalpha-directed process involving the migration of epithelial cells. MEKK1 expression in epithelial cells stimulates lamellipodia formation, a process required for cell movement. In addition, mouse embryo fibroblasts derived from MEKK1(-/-) mice are inhibited in their migration relative to MEKK1(+/+) fibroblasts. MEKK1 is required for JNK but not NF-kappaB activation in response to virus infection, microtubule disruption, and stimulation of embryonic stem cells with lysophosphatidic acid. MEKK1 is not required for TNFalpha or IL-1 regulation of JNK or NF-kappaB activation in macrophages or fibroblasts. Thus, MEKK1 senses microtubule integrity, contributes to the regulation of fibroblast and epithelial cell migration, and is required for activation of JNK but not NF-kappaB in response to selected stress stimuli.
Two types of highly purified, structurally defined LPS molecules prepared from Escherichia coli 0... more Two types of highly purified, structurally defined LPS molecules prepared from Escherichia coli 0111:B4 and Salmonella minnesota Re595 have been shown to differ significantly in their capacity to activate serum complement. However, both preparations, when injected i.v. into normal rabbits, rabbits depleted of C3, or rabbits genetically deficient in C6 produced almost identical decreases in blood pressure over a 5-hr period (post-injection). These changes were characterized by an initial decrease (20 to 30%) in blood pressure 30 to 60 min post-injection followed by a secondary fall in pressure beginning 120 min post-injection. No decreases in either C3 levels (radial immunodiffusion) or CH 50 values were detected after injection of either LPS preparation. The data suggests that the participation of C3 and the terminal complement components are not essential for LPS-induced hypotension. Additional support for this conclusion derives from experiments designed to examine directly the effect of complement activation in vivo on blood pressure.
Human and rabbit peripheral blood monocytes normally adhere to plastic tissue culture plates in v... more Human and rabbit peripheral blood monocytes normally adhere to plastic tissue culture plates in vitro when they are suspended in Hanks' media. Increasing amounts of autologous serum or heat-inactivated plasma in the cell suspensions prevented the adherence of both monocytes and lymphocytes. The inhibitory effect of plasma was separated into three areas of activity by chromatography on Sephacryl S-200. The profile of inhibitory activity did not coincide with the protein elution profile, suggesting that inhibition was not a nonspecific protein effect. A layer of adherent platelets overcame the inhibitory effect of plasma on monocyte adherence. Platelets selectively increased monocyte as opposed to lymphocyte adherence and this was specific for platelets in that neither neutrophils nor fibroblasts could substitute for platelets. Both plasma and platelets acted directly on monocytes.
Uploads
Papers by Peter Henson