CXC Chemokine Redundancy Ensures Local Neutrophil Recruitment during Acute Inflammation

• Published in: The American journal of pathology Vol. 159; no. 3; pp. 1149 - 1157
• Main Authors: Remick, Daniel George, Green, Liza Beth, Newcomb, David Eric, Garg, Sunir Jain, Bolgos, Gerald Lee, Call, Douglas Ruben
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.09.2001; ASIP; American Society for Investigative Pathology
• Subjects: Acute Disease; Animals; Biological and medical sciences; Cecum; Chemokines, CXC - metabolism; Fundamental and applied biological sciences. Psychology; Glycogen - pharmacology; Humans; Hydrochloric Acid; Inflammation; Inflammation - mortality; Inflammation - physiopathology; Interleukin-8 - genetics; Interleukin-8 - physiology; Ligation; Lung Diseases - chemically induced; Mice; Mice, Transgenic - genetics; Molecular and cellular biology; Morbidity; Neutrophil Infiltration - drug effects; Neutrophil Infiltration - physiology; Peritoneum - pathology; Punctures; Reference Values; Regular; Thioglycolates - pharmacology; Transgenes - physiology; Biochemical analysis; Acute; Rodentia; Granulocyte; Inflammation; Recruitment; Chemokine; Pathology; Vertebrata; Experimental disease; Mammalia; Mouse; Animal; Neutrophil; Molecular biology; CXC chemokine
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)61791-9

Previous publications demonstrated that elevated systemic levels of interleukin (IL)-8 decrease local neutrophil recruitment. We tested whether sustained, high plasma levels of IL-8 would prevent local inflammation after inflammatory insults. Mice carrying the transgene for human IL-8 were separated on the basis of their plasma levels of IL-8 into IL-8-positive (plasma levels >90 ng/ml) and IL-8-negative (IL-8 below detection). Presence of the IL-8 transgene did not improve survival or morbidity nor did it alter peritoneal neutrophil recruitment induced by the cecal ligation and puncture model of sepsis. In an acute lung injury model created by intratracheal injection of acid, IL-8-positive mice showed no reduction in alveolar neutrophil recruitment. There was no difference in the local recruitment of neutrophils when either thioglycollate or glycogen was injected intraperitoneally. We examined the chemotactic response to murine chemokines to test how neutrophil recruitment occurs in the setting of elevated plasma IL-8 and found that neutrophils from both IL-8-positive and -negative mice respond equally well to recombinant KC or macrophage inflammatory protein (MIP)-2. We measured KC and MIP-2 in the peritoneum after thioglycollate injection and demonstrated that IL-8-positive mice have significantly higher levels of the chemokines compared to the IL-8-negative mice. Antibody inhibition of KC and MIP-2 in the IL-8-positive mice significantly decreased peritoneal neutrophil recruitment in response to thioglycollate, clarifying their important role in the local neutrophil recruitment. Our data demonstrate that despite the presence of high plasma levels of IL-8, neutrophils may still be recruited to sites of local inflammation because of chemokine redundancy.