Selective transport of cytokine-induced neutrophil chemoattractant from the lung to the blood facilitates pulmonary neutrophil recruitment.
The CXC chemokines cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2) are potent neutrophil chemoattractants in rats. We have previously shown that CINC, unlike MIP-2 and most other proinflammatory cytokines, is elevated in the systemic circulation in response to an intratracheal (IT) challenge. Therefore, we hypothesized that CINC generated within the lung selectively enters the vascular compartment to facilitate pulmonary neutrophil recruitment. Rats were administered IT LPS, and plasma CINC and MIP-2 levels were measured 90 min and 4 h after injection, along with mRNA expression in lung, spleen, liver, and kidney. Ninety minutes and 4 h after IT LPS, CINC and MIP-2 mRNA expression were largely confined to lung homogenate, but of the two chemokines, only CINC was present in plasma. In separate experiments, rats received IT injections of recombinant CINC and/or MIP-2. Here, plasma levels of CINC, but not MIP-2, were significantly increased throughout the 4-h observation period. This finding was verified by individually administering (125)I-labeled forms of each chemokine. Instillation of recombinant MIP-2 or CINC into the lung increased the number of neutrophils recovered in bronchoalveolar lavage fluid at 4 h, and this effect was enhanced when both chemokines were administered together. In addition, intravenous (IV) CINC, but not IV MIP-2, increased pulmonary neutrophil recruitment in response to IT MIP-2. Our results show that CINC, in contrast to MIP-2, is selectively transported from the lung to the systemic circulation, where it promotes neutrophil migration into the lung in response to a chemotactic stimulus.
Quinton
Lee J
LJ
Department of Physiology, Louisiana State University Health Sciences Center, 1901 Perdido St., New Orleans, LA 70112. gbagby@lsuhsc.edu
Nelson
Steve
S
Zhang
Ping
P
Boé
Darren M
DM
Happel
Kyle I
KI
Pan
Weihong
W
Bagby
Gregory J
GJ
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D054426:Chemokine CXCL2; D019743:Chemokines, CXC / Q000097:blood* / Q000235:genetics / Q000493:pharmacokinetics*; D004731:Endotoxins / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000493:pharmacokinetics
D054426:Chemokine CXCL2; D019743:Chemokines, CXC; C513296:Cxcl2 protein, rat; D004731:Endotoxins; D036341:Intercellular Signaling Peptides and Proteins; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D011994:Recombinant Proteins