The human C3b receptor: function and role in human diseases.

The human C3b receptor (CR1) is a polymorphic glycoprotein which functions regulating the complement system by inhibiting the activation of C3 and C5, through its effect on their convertases, and serving as cofactor for factor I in mediating the degradation of C3b to its inactive fragment C3bi and further to C3d-g. The latter are then ligands for their respective receptors on leukocytes, CR3 and CR2. Additionally, CR1 on erythrocytes endows these cells with the capacity to deliver immune complexes (IC) to the reticuloendothelial system, resulting in their clearance from the circulation. On phagocytes, this receptor participates in the process of endocytosis of foreign particles. There is a wide inherited variation of CR1 expression on erythrocytes (CR1/E) of different individuals. Patients with diseases which feature elevated levels of IC, such as systemic lupus erythematosus, leprosy, and AIDS, have a marked decrease of CR1/E, which may result in an altered clearance. This reduction appears to be related to disease activity, and the most probable site for CR1/E loss is during the transfer of IC to macrophages. Healthy neutrophils increase tenfold their expression of CR1 in response to the effect of chemoattractant peptides. Neutrophils from patients with AIDS display an altered response to stimulation. This defect may be of relevance in the process of endocytosis.

Differential expression of Langerhans cells in the epidermis of patients with leprosy.

Eighteen patients with lepromatous leprosy (LL) showed a significant reduction (P less than 0.001) of Langerhans cells (LC) irrespective of whether the biopsies were obtained from involved (398 +/- 186) or healthy skin (304 +/- 98). The cells showed morphological changes consisting mainly of loss of dendritic processes. Twenty-four controls (age, sex and race matched) had a mean number of LC of 632 +/- 138. In tuberculoid patients (TT) significant differences were observed, depending on the site of biopsy. Nine biopsies from involved skin had 993 +/- 206 LC, whereas 11 from healthy skin had 448 +/- 96 (P less than 0.001). This difference was confirmed in six additional borderline tuberculoid (BT) and TT patients in whom biopsies were simultaneously obtained from involved (973 +/- 179) and uninvolved skin (498 +/- 99). In 10 patients with indeterminate leprosy the LC density did not differ from the control population (630 +/- 261). The expression of LC numbers in BT and TT patients may represent migration of these cells from healthy skin to involved areas or mobilization of a central pool. The low density found in LL patients could interfere with adequate presentation of mycobacterial antigens leading to tolerance. Alternatively the presence of T helper cells in TT infiltrates may produce factors that recruit LC; their absence in LL lesions may account for the decrease in LC expression.

Leprosy: altered complement receptors in disseminated disease.

We have studied the expression of the C3b receptor (CR1) on erythrocytes of 55 patients with Hansen's disease. We developed a radioimmunoassay utilizing a monoclonal antibody that recognized an epitope different from the C3b binding site, which therefore enabled us to measure total number of CR1 regardless of receptor occupancy. We observed that patients in the lepromatous pole of the disease had a mean of 310 CR1/erythrocyte, whereas the ones in the tuberculoid pole showed a mean of 577 CR1/erythrocyte; 77 normal controls had a mean of 512 CR1/erythrocyte. The number of C3b receptors on the cells of lepromatous patients was significantly decreased (p less than .001) when compared to the normal population or tuberculoid patients. The presence of receptors for the C3b fragment of complement (CR1) on the surface of human erythrocytes enables these cells to participate in a number of immune functions including the clearance of circulating immune complexes. These findings could bear importance in the ability of the host to clear immune complexes from the circulation in patients with lepromatous leprosy.