Functional characterization of the rat chemokine KC and its importance in neutrophil recruitment in a rat model of pulmonary inflammation.
Expression of mRNA for the neutrophil (PMN) chemokine, KC, in rat models of lung injury suggests a role for this chemokine in pulmonary inflammation. We addressed this hypothesis at the protein level by functionally characterizing recombinant rat KC (rKC) in vitro and in vivo. In vitro, rKC induced PMN chemotaxis and increased the expression of CD11b/CD18 on PMNs. Recombinant KC also induced a respiratory burst (quantitated by flow cytometry) in rat PMNs, similar to that caused by its human structural homologue, gro/melanoma growth-stimulating activity, on human PMNs, but less than that caused by IL-8 on human PMNs. Intratracheal instillation of rKC induced dose-dependent PMN influx into airspaces (average PMNs in bronchoalveolar lavage: vehicle = 1.5%, n = 4; rKC (1 microgram) = 11.5%, n = 2; rKC (10 micrograms) = 77.3%, n = 2). A neutralizing anti-KC Ab reduced the chemotactic activity of rat bronchoalveolar lavage fluid collected after the intratracheal administration of LPS (48.3 +/- 8% of control, n = 4). Anti-KC neutralizing Ab markedly inhibited PMN accumulation (71 +/- 6%) within the lungs in response to an intratracheal challenge of LPS. We conclude that rat KC is a major but not exclusive mediator of PMN activation and recruitment during LPS-induced pulmonary inflammation.
Frevert
C W
CW
Physiology Program, Harvard School of Public Health, Boston, MA 02115.
Huang
S
S
Danaee
H
H
Paulauskis
J D
JD
Kobzik
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D018821:CD18 Antigens / Q000096:biosynthesis; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000502:physiology* / Q000633:toxicity; D006133:Growth Substances / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced; D007322:Instillation, Drug; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008297:Male; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000502:physiology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016897:Respiratory Burst; D014132:Trachea
D018821:CD18 Antigens; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D016207:Cytokines; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D011993:Recombinant Fusion Proteins; C074302:keratinocyte-derived chemokines