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Background
CD14 is a pattern-recognition receptor and exists as two distinct forms: as a glycosyl-phosphatidylinositol (GPI) - anchored membrane protein on the surface of monocytes, macrophages and neutrophils and as a monocyte or liver-derived serum soluble protein (sCD14) lacking the GPI anchor [1]. Soluble CD14 is an acute phase protein [2], but is also found in normal serum at microgram concentrations [3], and confers sensitivity to a gram-negative bacterial cell wall component, i.e. lipopolysaccharide (LPS), for cells lacking membrane CD14, such as endothelial and epithelial cells [4]. Together with LPS and LPS-binding protein, CD14 forms a ligand that interacts with the toll-like receptor - 4 (TLR-4)/MD-2 receptor complex and leads to activation of innate host defense mechanisms, stimulating numerous Th1 proinflammatory cytokines, including tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) [5]. Recently, it has been suggested that CD14 also can interact with other pathogen-associated molecular patterns (PAMPs) such as acylated lipoproteins and peptidioglycan from gram-positive bacteria, and can participate in the formation of multi-receptor complexes other than TLR-4, e.g. TLR-1, -2 and -6 [6].
Farming environments are highly contaminated with airborne inhalable organic dust [7, 8], which contains PAMPs, including gram-negative and gram-positive bacterial components [9, 10]. Forty % of these dust particles are in the respirable range with a median diameter of 4 ?m or less, which may be deposited at the level of the terminal bronchioles and alveoli [7, 11]. Chronic inhalation of complex organic dust is implicated in respiratory disease development and severity, including rhinitis, sinusitis, asthma-like syndrome, organic dust toxic syndrome, chronic bronchitis, and chronic obstructive pulmonary disease (COPD) [12]. Several studies associate LPS levels in the agricultural environment with adverse respiratory health outcomes. In healthy individuals, inhalation of purified LPS induces dose-related symptoms, a decrease in lung function and diffusion capacity, airway obstruction and both bronchial and systemic inflammation [13-17].
While these studies suggest an important role of LPS in respiratory disease pathogenesis, the function of sCD14, a critical receptor for LPS, in host defense and respiratory disease among agricultural workers has not been defined. In fact, no large-scale comprehensive studies have examined the relationship of sCD14 concentrations with measures of lung function in occupationally- or non-occupationally- exposed individuals. The limited numbers of small studies in non-occupationally exposed adults have...