Conversely, IC-loaded red cells have been reported to interact with macrophages leading to production of the pro-inflammatory cytokine interleukin (IL)-1 [12]. The level of expression of CR1 on red cells is influenced by a variety of factors. There are known quantitative polymorphisms (H and L) that can result in
low (LL), medium (HL) or high (HH) expression [5]. In addition, the level of CR1 is known to decline with the age of red cells [13,14] and can vary with the age of the host [15], as well as his/her health status [16]. For instance, individuals with certain conditions leading to formation of ICs such as malaria or systemic lupus erythematosus (SLE) tend to have lower CR1 on their red cells [15–19]. The variability in the level of red cell CR1 expression suggests that individuals at selleck kinase inhibitor either end of the expression spectrum may suffer deleterious consequences of IC-mediated diseases. Low expressors may be less equipped to remove ICs from circulation, leading to IC deposition in tissues and the consequent inflammatory response. Conversely, high expressors may trap ICs on red cells too effectively which, under certain circumstances such as in the slow circulation of the spleen or in congested capillaries of malaria-infected individuals, may cross-link
Fcγ receptors on monocyte/macrophages leading to production of proinflammatory cytokines [9–11,20]. To investigate the dual role of red cell CR1 on modulating the IC-mediated production of tumour necrosis factor CAL-101 in vivo (TNF)-α by macrophages and how this is affected by the CR1 expression level, we selected individuals with low, medium and high red cell CR1 expression. We then measured the ability of their red cells to enhance or inhibit TNF-α production
by macrophages in vitro in the presence ICs. This study was part of a larger cross-sectional survey to study the relationship between red cell complement regulatory protein expression, age and C3b deposition [21]. It was approved by and executed in accordance with guidelines of the Human Use Research Committee of the Walter Reed Army Institute of Research and of the Kenya National Ethics Review Committee, Kenya Medical Research Institute. Informed consent was obtained Urocanase from each participant or from the parent or guardian of participants under 18 years of age. The study was carried out in Kombewa Division, a malaria holoendemic region of the Lake Victoria basin in western Kenya, where most individuals are of the Luo ethnic group. The eligibility criteria and screening procedures were detailed previously [21]. Briefly, any person resident in the study area, male or female, aged 45 years or younger was eligible to participate in the study. Only healthy, malaria-negative individuals, as confirmed by a standardized physical examination and thick and thin Giemsa-stained blood smears, served as blood donors.