Asthma and endotoxin: lipopolysaccharide-binding protein and soluble CD14 in bronchoalveolar compartment

Abstract

In allergic asthma, inhalation of antigen provokes an early increase in microvascular permeability with protein extravasation and a delayed recruitment of inflammatory cells. We showed that similar concentrations of lipopolysaccharide (LPS) are present in bronchoalveolar lavage fluid (BALF) in 12 subjects without asthma (86.5 +/- 53.8 pg/ml) and 12 subjects with mild asthma (111 +/- 37.0 pg/ml). These LPS levels are insufficient to stimulate cytokine release without accessory molecules. BALF obtained 24 h after segmental ragweed antigen challenge in 11 asthmatics allergic to ragweed contained increased levels of two LPS accessory molecules compared with preantigen BALF, 158-fold more LPS-binding protein (LBP) 4.83 +/- 2.02 vs. 742 +/- 387 ng/ml; P < 0.03) and 31.6-fold more soluble CD14 (sCD14) (3.45 +/- 1.04 vs. 110 +/- 51.6 ng/ml; P < 0.02). Postantigen BALF enhanced binding of fluorescein-conjugated LPS to CD14-bearing THP-1 cells and supported LPS-induced non-CD14-bearing endothelial cell expression of intercellular adhesion molecule-1 and interleukin-6, indicating functional LBP and sCD14. We suggest that extravasation of LBP and sCD14 into the bronchoalveolar compartment after antigen inhalation may enhance the capacity of inhaled or aspirated LPS to activate an inflammatory cascade that may amplify the inflammatory response to inhaled antigen in some asthmatics.

Toll-Like Receptor (TLR)2 and TLR4 in Human Peripheral Blood Granulocytes: A Critical Role for Monocytes in Leukocyte Lipopolysaccharide Responses

“…However, lack of membrane CD14 is not necessarily a bar to LPS responsiveness (58), and soluble CD14 is present in FCS as used in all our assays (59), which has been shown to enable LPS responses in some, but not all, CD14-negative cells (60,61). Soluble CD14 is effectively delivered to sites of allergic inflammation (62), and the presence of TLR2 and TLR4 on the basophil suggests that LPS responsiveness in this cell type may be inducible at sites of inflammation. Due to a lack of reagents, we were unable to investigate expression of the LPS coreceptor MD-2 in basophils, but it is also possible that a lack of MD-2 contributes to their nonresponsiveness to LPS.…”

IL-9 and IL-13 Production by Activated Mast Cells Is Strongly Enhanced in the Presence of Lipopolysaccharide: NF-κB Is Decisively Involved in the Expression of IL-9

“…Interestingly, inflammatory and bronchial obstructive responses to inhalation of endotoxin in asthmatic patients have been described, and it has been supposed that bacterial Ags can potentiate the action of inhalant Ags (60 -62). In asthmatics, extravasation of LPS binding protein and soluble CD14 into the bronchoalveolar compartment after allergen inhalation has also been reported, implying a role for LPS in amplification of the inflammatory response (63)(64)(65). During late asthmatic reactions, an accumulation of mast cells occurs in lung in parallel with an increased IgE level in serum that promotes IgEmediated activation of mast cells.…”

The Presence of CD14 Overcomes Evasion of Innate Immune Responses by VirulentFrancisella tularensisin Human Dendritic Cells In Vitro and Pulmonary Cells In Vivo

“…abundant in the airways of healthy mammals (22,51). Alveolar macrophages and airway DC are the primary targets of Francisella infection following inhalation of the bacterium during the first few days of infection, and these cells have both functional and phenotypic properties that are similar to those of human dendritic cells derived from peripheral blood (5,11,12,28,29,36,56).…”