Acid and particulate-induced aspiration lung injury in mice: importance of MCP-1

• Published in: American journal of physiology. Lung cellular and molecular physiology 2005-07, Vol.289 (1), p.L134-L143
• Main Authors: Raghavendran, Krishnan, Davidson, Bruce A, Mullan, Barbara A, Hutson, Alan D, Russo, Thomas A, Manderscheid, Patricia A, Woytash, James A, Holm, Bruce A, Notter, Robert H, Knight, Paul R
• Format: Article
• Language: English
• Subjects: Animals; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Cytokines - biosynthesis; Granuloma - metabolism; Granuloma - pathology; Hydrochloric Acid - toxicity; Lung - metabolism; Lung - pathology; Mice; Mice, Knockout; Pneumonia, Aspiration - genetics; Pneumonia, Aspiration - metabolism; Pneumonia, Aspiration - pathology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00390.2004

Departments of 1 Surgery, 2 Anesthesiology, 3 Medicine, 4 Pathology, and 5 Pediatrics, and 6 School of Preventive Medicine, University at Buffalo-State University of New York, Buffalo; and 7 Department of Pediatrics, University of Rochester, Rochester, New York Submitted 21 October 2004 ; accepted in final form 11 March 2005 A model of aspiration lung injury was developed in WT C57BL/6 mice to exploit genetically modified animals on this background, i.e., MCP-1(–/–) mice. Mice were given intratracheal hydrochloric acid (ACID, pH 1.25), small nonacidified gastric particles (SNAP), or combined acid plus small gastric particles (CASP). As reported previously in rats, lung injury in WT mice was most severe for "two-hit" aspiration from CASP (40 mg/ml particulates) based on the levels of albumin, leukocytes, TNF- , IL-1 , IL-6, MCP-1, KC, and MIP-2 in bronchoalveolar lavage (BAL) at 5, 24, and 48 h. MCP-1(–/–) mice given 40 mg/ml CASP had significantly decreased survival compared with WT mice (32% vs. 80% survival at 24 h and 0% vs. 72% survival at 48 h). MCP-1(–/–) mice also had decreased survival compared with WT mice for CASP aspirates containing reduced particulate doses of 10–20 mg/ml. MCP-1(–/–) mice given 5 mg/ml CASP had survival similar to WT mice given 40 mg/ml CASP. MCP-1(–/–) mice also had differing responses from WT mice for several inflammatory mediators in BAL (KC or IL-6 depending on the particle dose of CASP and time of injury). Histopathology of WT mice with CASP (40 mg particles/ml) showed microscopic areas of compartmentalization with prominent granuloma formation by 24 h, whereas lung tissue from MCP-1(–/–) mice had severe diffuse pneumonia without granulomas. These results indicate that MCP-1 is important for survival in murine aspiration pneumonitis and appears to act partly to protect uninjured lung regions by promoting isolation and compartmentalization of tissue with active inflammation. monocyte chemoattractant protein-1; aspiration lung injury; acid aspiration; gastric particle aspiration; combined acid and gastric particle aspiration Address for reprint requests and other correspondence: P. R Knight, Dept. of Anesthesiology, SUNY at Buffalo, 245 Biomedical Research Bldg., 3435 Main St., Buffalo, NY 14214 (E-mail: pknight{at}buffalo.edu )