No abstract

Complement activation in the kidney after ischemia/reperfusion (I/R) seems to occur primarily via the alternative complement pathway. The ability of an inhibitory mAb to mouse factor B, a necessary component of the alternative pathway, to protect mice from ischemic acute renal failure was tested. Treatment with the mAb prevented the deposition of C3b on the tubular epithelium and the generation of systemic C3a after renal I/R. Treated mice had significantly lower increases in serum urea nitrogen and developed significantly less morphologic injury of the kidney after I/R. For gaining insight into potential mechanisms of protection, the activity of caspases within the kidney also was measured, and it was found that caspases-2, -3, and -9 increased in a complement-dependent manner after renal I/R. Apoptotic cells were detected by terminal deoxynucleotidyl transferase catalyzed labeling of DNA fragments, and mice in which the alternative pathway was inhibited demonstrated significantly less apoptosis than control mice. Thus, use of an inhibitory mAb to mouse factor B effectively prevented activation of complement in the kidney after I/R and protected the mice from necrotic and apoptotic injury of the tubules. T he alternative pathway of complement is activated after ischemia/reperfusion (I/R) of the kidneys in rodents and humans (1,2), and complement deficiency protects mice from the full development of ischemic acute renal failure (ARF) (2,3). Complement activation by the classical and lectin pathways has been demonstrated after I/R of the heart (4), intestine (5,6), and skeletal muscle (7). Mannose-binding lectin is deposited in the postischemic kidney (8), perhaps indicating activation of this pathway. Complement activation after I/R of the kidney is critically dependent on an intact alternative pathway (2,3), however, and does not require the protein C4 (3). Selective inhibition of the alternative pathway, therefore, should confer protection against the development of ischemic ARF while leaving the classical and lectin pathways intact.Renal I/R results in both epithelial cell necrosis and apoptosis (9). Although necrosis is often the more prominent morphologic finding, inhibition of apoptosis has been shown to protect mice from ischemic ARF (10). The caspases are a group of cysteine proteases that execute many of the processes that are necessary for cellular apoptosis (11). Studies have demonstrated that complement activation directly activates caspases within renal cells (12) and may also induce caspase activity within other tissues after I/R (13). Furthermore, the use of an anti-C5 antibody (which prevents formation of C5a and the membrane attack complex) has been shown to prevent the development of apoptosis after renal (14) and cardiac (13) I/R. Thus, there is reason to suspect that complement activation in the kidney after I/R mediates the development of apoptosis through the caspases and that this is an important mechanism of complement-mediated injury to the kidney.We recently developed an inhibitory mAb ...

The complement system is one of the major ways by which the body detects injury to self cells, and the alternative pathway of complement is rapidly activated within the tubulointerstitium after renal ischemia/reperfusion (I/R). In the current study, we investigate the hypothesis that recognition of tubular injury by the complement system is a major mechanism by which the systemic inflammatory response is initiated. Gene array analysis of mouse kidney following I/R initially identified MIP-2 (CXCL2) and keratinocyte-derived chemokine (KC or CXCL1) as factors that are produced in a complement-dependent fashion. Using in situ hybridization, we next demonstrated that these factors are expressed in tubular epithelial cells of postischemic kidneys. Mouse proximal tubular epithelial cells (PTECs) in culture were then exposed to an intact alternative pathway and were found to rapidly produce both chemokines. Selective antagonism of the C3a receptor significantly attenuated production of MIP-2 and KC by PTECs, whereas C5a receptor antagonism and prevention of membrane attack complex (MAC) formation did not have a significant effect. Treatment of PTECs with an NF-κB inhibitor also prevented full expression of these factors in response to an intact alternative pathway. In summary, alternative pathway activation after renal I/R induces production of MIP-2 and KC by PTECs. This innate immune system thereby recognizes hypoxic injury and triggers a systemic inflammatory response through the generation of C3a and subsequent activation of the NF-κB system.

In this retrospective study, the authors describe the clinical, histologic and laboratory features of 15 cases of chilblain or perniotic lupus. In winter, the patients (14 women, 1 man) develop chilblain-like lesions, chiefly in the toes (8 times) and fingers (11 times). Histologic features are identical to those of discoid lupus erythematosus. The damaged skin gives a positive fluorescent band test. Usually, these lesions occur in association with discoid lupus of the face. However, in 8 patients, they were the only cutaneous sign of lupus. This form of lupus can evolve to a systemic form, as was the case with 3 patients.

It is crucial for refugee service providers to understand the family planning knowledge, attitudes, and practices of refugee women following third country resettlement. Using an ethnographic approach rooted in Reproductive Justice, we conducted six focus groups that included 66 resettled Somali and Congolese women in a western United States (US) metropolitan area. We analyzed data using modified grounded theory. Three themes emerged within the family planning domain: (a) concepts of family, (b) fertility management, and (c) unintended pregnancy. We contextualized these themes within existing frameworks for refugee cultural transition under the analytic paradigms of “pronatalism and stable versus evolving family structure” and “active versus passive engagement with family planning.” Provision of just and equitable family planning care to resettled refugee women requires understanding cultural relativism, social determinants of health, and how lived experiences influence family planning conceptualization. We suggest a counseling approach and provider practice recommendations based on our study findings.