Functional contribution of CXCR2 to lung injury after aspiration of acid and gastric particulates.
The effects of individual ELR+ CXC chemokines have been documented in experimental models of acid aspiration. However, aspiration lung injury would be influenced by the combined effects of these chemokines and other factors related to their function. Therefore, the role of the chemokine receptor CXCR2 was examined in lung injury induced by aspiration of acid and acid with gastric particulates. Anesthetized mice were given intratracheal injections of saline, acid solution, or acid containing gastric particles. Within 6 h, bronchoalveolar lavage fluid neutrophils and albumin increased relative to the severity of the insult. Immunohistochemistry and RT-PCR demonstrated striking increases in pulmonary expression of CXCR2 after aspiration. In CXCR2-deficient mice, neutrophil recruitment to airways was significantly reduced after aspiration of either acid or acid with particles. However, lung injury scores were unaffected in Ccr2-/- mice in the acid + particles group. Esterase-stained lung tissue demonstrated that focal aggregates of inflammatory cells contained neutrophils in the Ccr2-/- mice. These studies suggest CXCR2 and its ligands are dominant mediators of neutrophil recruitment to airways after aspiration. However, CXCR2-independent mechanisms recruit neutrophils into areas of cellular aggregation after aspiration of acidified gastric particulates.
Nemzek
Jean A
JA
Unit for Laboratory Animal Medicine, Department of Pathology, University of Michigan, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA. jnemzek@umich.edu
Abatan
Omorodola
O
Fry
Christopher
C
Mattar
Aladdein
A
D000143:Acids; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D055370:Lung Injury / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D052638:Particulate Matter / Q000009:adverse effects*; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053120:Respiratory Aspiration / Q000150:complications* / Q000473:pathology*
D000143:Acids; D057134:Antibodies, Neutralizing; D018925:Chemokines; D052638:Particulate Matter; D012333:RNA, Messenger; D023063:Receptors, Interleukin-8B