title: Neutrophil modulation of the pulmonary chemokine response to lipopolysaccharide.
abstract: When cells within the intrapulmonary compartment are exposed to pathogens or their products such as lipopolysaccharide, they produce CXC chemokines in order to attract circulating neutrophils into the lower respiratory tract. Previous studies have shown that as neutrophils (PMNs) enter the lung, bronchoalveolar lavage (BAL) chemokine levels are decreased. In this study, we determined the intrapulmonary and systemic responses to two important rat chemokines, cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2), to intratracheal (i.t.) LPS (100 microg in 0.5 mL of phosphate-buffered saline) under neutropenic (cyclophosphamide [CPA]) and neutrophilic (G-CSF) conditions. By 4 h after i.t. LPS, CPA pretreatment decreased PMN recruitment 83% and G-CSF increased PMN recruitment 91% compared with recruitment into the lung in vehicle-pretreated rats (42.7 +/- 19.3 million PMNs). Neutropenic rats had increased CINC and MIP-2 concentrations in BAL fluid 4 h after i.t. LPS when compared with levels seen in vehicle controls (P < 0.05). In vitro LPS-stimulated chemokine production by alveolar macrophages obtained from CPA- and vehicle-pretreated animals did not differ. The increase in BAL fluid chemokine levels in neutropenic rats corresponded to increased chemotaxis of neutrophils to BAL fluid from CPA-pretreated rats as compared with the chemotaxis response of PMN to BAL fluid from vehicle-pretreated rats. In contrast, G-CSF enhancement of neutrophil recruitment decreased chemotactic activity of BAL fluid collected 4 h after i.t. LPS. These data show that as neutrophils are recruited into the lung, they alter chemokine levels, which most likely serves to down-regulate the inflammatory response.
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Holmes
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Steve
authors.initials: S
authors.lastname: Nelson
authors.forename: Warren R
authors.initials: WR
authors.lastname: Summer
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bagby
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018925:Chemokines; D008070:Lipopolysaccharides