Mechanism for the inflammatory response in primate lungs. Demonstration and partial characterization of an alveolar macrophage derived chemotactic factor with preferential activity for polymorphonuclear leukocytes

J. A. Kazmierowski, J. I. Gallin, Herbert Reynolds

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Abstract

Approximately 4 h after an initial bronchoalveolar lavage (BAL) of a primate's lung, an appreciable number of polymorphonuclear leukocytes (PMN's) were noted to accumulate in respiratory fluids when lavage was repeated. Whereas, alveolar macrophages (90%) and lymphocytes (7%) were the principal respiratory cells recovered initially from lavage fluid, later samples contained 45-90% PMNs. To explain the observed ingress of PMNs into lung fluids, concentrated BAL fluid was tested for chemoattractant activity. Such obtained 4 and 24 h after an initial lavage contained material that produced directed migration (chemotaxis) for PMNs and mononuclear cells isolated from peripheral blood of normal donors. Gel filtration chromatography of BAL disclosed two peaks of chemotactic activity in the effluent fractions. Material from the column with an estimated molecular weight of 15,000 daltons was chemotactic for both PMNs and mononuclear cells. Because it was susceptible to inactivation with antiserum against the fifth component of complement, resistant to heating, and unaffected by antiserum against C3, this factor was considered analogous to the cleavage product of the fifth component of complement, C5a. In addition chemotactic activity for PMNs only was contained in an effluent peak having a molecular weight of about 5,000 daltons. This material was heat labile but unaffected by antisera to complement components. To locate the possible source of these factors in respiratory fluid, in vitro cultures of alveolar macrophages were established. These cells, whether stimulated by phagocytosis of opsonized bacteria or merely by attachment to a glass surface, produced chemotactic material which had physical characteristics similar to the small molecular weight material in BAL. Moreover, it induced preferential chemotaxis for PMNs. Thus, in primate lungs, at least two chemotactic substances may generate an inflammatory response; one which is a fragment of the complement component C5 and another small molecular weight factor which is released from alveolar macrophages.

Original languageEnglish (US)
Pages (from-to)273-281
Number of pages9
JournalJournal of Clinical Investigation
Volume59
Issue number2
DOIs
StatePublished - Jan 1 1977

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Alveolar Macrophages
Interleukin-8
Primates
Therapeutic Irrigation
Neutrophils
Bronchoalveolar Lavage
Molecular Weight
Immune Sera
Lung
Chemotaxis
Complement C5a
Complement C5
Chemotactic Factors
Bronchoalveolar Lavage Fluid
Blood Donors
Phagocytosis
Heating
Glass
Gel Chromatography
Hot Temperature

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

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title = "Mechanism for the inflammatory response in primate lungs. Demonstration and partial characterization of an alveolar macrophage derived chemotactic factor with preferential activity for polymorphonuclear leukocytes",
abstract = "Approximately 4 h after an initial bronchoalveolar lavage (BAL) of a primate's lung, an appreciable number of polymorphonuclear leukocytes (PMN's) were noted to accumulate in respiratory fluids when lavage was repeated. Whereas, alveolar macrophages (90{\%}) and lymphocytes (7{\%}) were the principal respiratory cells recovered initially from lavage fluid, later samples contained 45-90{\%} PMNs. To explain the observed ingress of PMNs into lung fluids, concentrated BAL fluid was tested for chemoattractant activity. Such obtained 4 and 24 h after an initial lavage contained material that produced directed migration (chemotaxis) for PMNs and mononuclear cells isolated from peripheral blood of normal donors. Gel filtration chromatography of BAL disclosed two peaks of chemotactic activity in the effluent fractions. Material from the column with an estimated molecular weight of 15,000 daltons was chemotactic for both PMNs and mononuclear cells. Because it was susceptible to inactivation with antiserum against the fifth component of complement, resistant to heating, and unaffected by antiserum against C3, this factor was considered analogous to the cleavage product of the fifth component of complement, C5a. In addition chemotactic activity for PMNs only was contained in an effluent peak having a molecular weight of about 5,000 daltons. This material was heat labile but unaffected by antisera to complement components. To locate the possible source of these factors in respiratory fluid, in vitro cultures of alveolar macrophages were established. These cells, whether stimulated by phagocytosis of opsonized bacteria or merely by attachment to a glass surface, produced chemotactic material which had physical characteristics similar to the small molecular weight material in BAL. Moreover, it induced preferential chemotaxis for PMNs. Thus, in primate lungs, at least two chemotactic substances may generate an inflammatory response; one which is a fragment of the complement component C5 and another small molecular weight factor which is released from alveolar macrophages.",
author = "Kazmierowski, {J. A.} and Gallin, {J. I.} and Herbert Reynolds",
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T1 - Mechanism for the inflammatory response in primate lungs. Demonstration and partial characterization of an alveolar macrophage derived chemotactic factor with preferential activity for polymorphonuclear leukocytes

AU - Kazmierowski, J. A.

AU - Gallin, J. I.

AU - Reynolds, Herbert

PY - 1977/1/1

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N2 - Approximately 4 h after an initial bronchoalveolar lavage (BAL) of a primate's lung, an appreciable number of polymorphonuclear leukocytes (PMN's) were noted to accumulate in respiratory fluids when lavage was repeated. Whereas, alveolar macrophages (90%) and lymphocytes (7%) were the principal respiratory cells recovered initially from lavage fluid, later samples contained 45-90% PMNs. To explain the observed ingress of PMNs into lung fluids, concentrated BAL fluid was tested for chemoattractant activity. Such obtained 4 and 24 h after an initial lavage contained material that produced directed migration (chemotaxis) for PMNs and mononuclear cells isolated from peripheral blood of normal donors. Gel filtration chromatography of BAL disclosed two peaks of chemotactic activity in the effluent fractions. Material from the column with an estimated molecular weight of 15,000 daltons was chemotactic for both PMNs and mononuclear cells. Because it was susceptible to inactivation with antiserum against the fifth component of complement, resistant to heating, and unaffected by antiserum against C3, this factor was considered analogous to the cleavage product of the fifth component of complement, C5a. In addition chemotactic activity for PMNs only was contained in an effluent peak having a molecular weight of about 5,000 daltons. This material was heat labile but unaffected by antisera to complement components. To locate the possible source of these factors in respiratory fluid, in vitro cultures of alveolar macrophages were established. These cells, whether stimulated by phagocytosis of opsonized bacteria or merely by attachment to a glass surface, produced chemotactic material which had physical characteristics similar to the small molecular weight material in BAL. Moreover, it induced preferential chemotaxis for PMNs. Thus, in primate lungs, at least two chemotactic substances may generate an inflammatory response; one which is a fragment of the complement component C5 and another small molecular weight factor which is released from alveolar macrophages.

AB - Approximately 4 h after an initial bronchoalveolar lavage (BAL) of a primate's lung, an appreciable number of polymorphonuclear leukocytes (PMN's) were noted to accumulate in respiratory fluids when lavage was repeated. Whereas, alveolar macrophages (90%) and lymphocytes (7%) were the principal respiratory cells recovered initially from lavage fluid, later samples contained 45-90% PMNs. To explain the observed ingress of PMNs into lung fluids, concentrated BAL fluid was tested for chemoattractant activity. Such obtained 4 and 24 h after an initial lavage contained material that produced directed migration (chemotaxis) for PMNs and mononuclear cells isolated from peripheral blood of normal donors. Gel filtration chromatography of BAL disclosed two peaks of chemotactic activity in the effluent fractions. Material from the column with an estimated molecular weight of 15,000 daltons was chemotactic for both PMNs and mononuclear cells. Because it was susceptible to inactivation with antiserum against the fifth component of complement, resistant to heating, and unaffected by antiserum against C3, this factor was considered analogous to the cleavage product of the fifth component of complement, C5a. In addition chemotactic activity for PMNs only was contained in an effluent peak having a molecular weight of about 5,000 daltons. This material was heat labile but unaffected by antisera to complement components. To locate the possible source of these factors in respiratory fluid, in vitro cultures of alveolar macrophages were established. These cells, whether stimulated by phagocytosis of opsonized bacteria or merely by attachment to a glass surface, produced chemotactic material which had physical characteristics similar to the small molecular weight material in BAL. Moreover, it induced preferential chemotaxis for PMNs. Thus, in primate lungs, at least two chemotactic substances may generate an inflammatory response; one which is a fragment of the complement component C5 and another small molecular weight factor which is released from alveolar macrophages.

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