Expression of macrophage inflammatory protein-2 and KC mRNA in pulmonary inflammation.
This study sought to test the hypothesis that expression of mRNA for two cytokines, macrophage inflammatory protein-2 (MIP-2) and the KC gene product, is induced in rat lung cells during inflammatory responses in vitro and in vivo. Macrophage inflammatory protein-2 and KC are members of the platelet-factor 4 (PF-4) cytokine superfamily that cause marked neutrophil chemotaxis and activation in vitro. To investigate expression of the genes for MIP-2 and KC in rat models of lung injury, cDNA probes for these cytokines in the rat were made from polymerase chain reaction (PCR) products generated using mouse sequence-derived primers. Sequence analysis of these cDNAs showed marked homology to known murine sequences (89% and 92% MIP-2 and KC, respectively). These cDNAs were first used to study the expression of these two genes in rat alveolar macrophages (AMs) in vitro by Northern blot hybridization. Lipopolysaccharide (LPS) treatment of rat AMs in vitro caused marked increases in mRNA for both KC and MIP-2 within 30 minutes, which persisted through the 6 hours measured. To study expression during inflammation in vivo, rats were treated with LPS by intratracheal instillation. Bronchoalveolar lavage (BAL) cells and whole trachea homogenates were analyzed. There was a marked and rapid increase in MIP-2 and KC mRNA levels within both BAL cells and trachea homogenates after LPS instillation. The results support the hypothesis that MIP-2 and KC cytokines contribute to neutrophil chemotaxis and activation in this rat model of acute pulmonary inflammation.
Huang
S
S
Department of Environmental Health, School of Public Health, Boston, Massachusetts.
Paulauskis
J D
JD
Godleski
J J
JJ
Kobzik
L
L
D000818:Animals; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines / Q000378:metabolism*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D015846:Monokines / Q000378:metabolism*; D011014:Pneumonia / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014132:Trachea / Q000378:metabolism
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D008070:Lipopolysaccharides; D015846:Monokines; D012333:RNA, Messenger; C074302:keratinocyte-derived chemokines