Alpha chemokines regulate direct lung ischemia-reperfusion injury.

Abstract

BACKGROUND:

Alpha chemokines function predominantly to recruit and activate neutrophils, which are important effectors of acute lung injury. This study evaluated whether blockade of 2 potent alpha chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC), is protective against lung ischemia-reperfusion injury in a warm in situ hilar clamp model.

METHODS:

Left lungs of Long-Evans rats underwent normothermic ischemia for 90 minutes and reperfusion for up to 4 hours. Treated animals received antibodies to MIP-2 or CINC immediately prior to reperfusion. Lung injury was quantitated by vascular permeability to (125)I-radiolabeled bovine serum albumin, lung tissue neutrophil sequestration (myeloperoxidase [MPO] content), and alveolar leukocyte content in bronchoalveolar lavage (BAL) fluid. CINC and MIP-2 mRNA expression were assessed by northern blot, while ribonuclease protection assays were performed to evaluate mRNA expression for a number of early response cytokines. MIP-2 and CINC protein expression in injured lungs was determined by immunoblotting.

RESULTS:

Treatment with antibodies to CINC or MIP-2 was associated with significant protection against increases in vascular permeability, MPO content and alveolar leukocyte sequestration in injured lungs. Expression of CINC and MIP-2 mRNA peaked after 2 hours of reperfusion in injured lungs, and protein levels were evident on immunoblotting after 3 hours of reperfusion. Neither CINC nor MIP-2 blockade appeared to modulate cytokine mRNA expression.

CONCLUSIONS:

CINC and MIP-2 are important mediators involved in direct lung ischemia-reperfusion injury. They appear to function by modulating neutrophil recruitment, but not inflammatory cytokine release.

• Authors: Alexander S Farivar, Baiya Krishnadasan, Babu V Naidu, Steven M Woolley, Edward D Verrier, Michael S Mulligan
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 23 Issue 5 Pg. 585-91 (May 2004) ISSN: 1053-2498 [Print] United States
• PMID: 15135375 (Publication Type: Journal Article)

Chemical References

• Chemokine CXCL2
• Chemokines, CXC
• Cxcl2 protein, rat
• Intercellular Signaling Peptides and Proteins
• Peroxidase

Topics

• Animals
• Blotting, Northern
• Blotting, Western
• Bronchoalveolar Lavage
• Capillary Permeability (physiology)
• Chemokine CXCL2
• Chemokines, CXC (analysis, physiology)
• Disease Models, Animal
• Intercellular Signaling Peptides and Proteins (analysis, physiology)
• Lung (blood supply)
• Peroxidase (analysis)
• Rats
• Rats, Long-Evans
• Reperfusion Injury (physiopathology)