Role of major histocompatibility complex class II expression by non-hematopoietic cells in autoimmune and inflammatory disorders: facts and fiction.

It is well established that interactions between CD4(+) T cells and major histocompatibility complex class II (MHCII) positive antigen-presenting cells (APCs) of hematopoietic origin play key roles in both the maintenance of tolerance and the initiation and development of autoimmune and inflammatory disorders. In sharp contrast, despite nearly three decades of intensive research, the functional relevance of MHCII expression by non-hematopoietic tissue-resident cells has remained obscure. The widespread assumption that MHCII expression by non-hematopoietic APCs has an impact on autoimmune and inflammatory diseases has in most instances neither been confirmed nor excluded by indisputable in vivo data. Here we review and put into perspective conflicting in vitro and in vivo results on the putative impact of MHCII expression by non-hematopoietic APCs--in both target organs and secondary lymphoid tissues--on the initiation and development of representative autoimmune and inflammatory disorders. Emphasis will be placed on the lacunar status of our knowledge in this field. We also discuss new mouse models--developed on the basis of our understanding of the molecular mechanisms that regulate MHCII expression--that constitute valuable tools for filling the severe gaps in our knowledge on the functions of non-hematopoietic APCs in inflammatory conditions.

Reoperation and the centrifugal pump?

Postperfusion syndrome is still a problem in long cardiac operations using extracorporeal circulation (ECC). To evaluate whether or not centrifugal blood pumping during open heart surgery is beneficial, a randomized, prospective study was undertaken of 50 consecutive patients undergoing elective coronary artery bypass grafting. The patients were divided into two groups of 25 each. In group 1 a centrifugal pump (Biomedicus) was used as arterial blood pump, while in group 2 a roller pump (Stöckert) was used. The two groups did not differ significantly and the number of variables during surgery was kept low (identical perfusion set, two surgeons, minimal cardiotomy suction). The parameters studied included the cellular elements of the blood and components indicating their functional integrity, such as PMN-elastase, plasma hemoglobin, beta-thromboglobulin, and thrombin-antithrombin III complex and D-dimer as representatives for activated coagulation and secondary fibrinolysis. Blood and urine samples were taken every 15 min during ECC, on arrival in the intensive care unit, and 1, 3, 6, 12, and 24 h thereafter. No difference between the groups was found in regard to bypass time, ECC flow and volume, fluid balance, and clinical outcome. Significant differences in favor of group 1 were found in plasma hemoglobin (P less than 0.05), beta-thromboglobulin (P less than 0.01), D-dimer (P less than 0.05), and platelet counts (P less than 0.5). These differences were clearly ECC-time-dependent and became statistically significant after 90 min bypass. We conclude that roller pumps still can be safely used for standard cardiac procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Routine extracorporeal circulation with a centrifugal or roller pump.

In a randomized, prospective clinical trial, 50 patients undergoing elective coronary artery bypass grafting (CABG) were divided into two groups of 25 each. Group I had a centrifugal pump (CP, Biomedicus) and Group II a roller pump (RP, Stöckert) as the arterial line. Neither group differed significantly, and variables during surgery were kept to a minimum. The parameters studied included the cellular blood elements and their components, such as PMN-elastase (PMN-E), plasma hemoglobin (pHb), beta-thromboglobulin (beta-TG), and D-dimer (D-D) and thrombin-antithrombin III complex (TAT) as indicators for activated coagulation. Blood and urine samples were taken at induction of anesthesia, every 15 minutes throughout extracorporeal circulation (ECC), at arrival in the ICU, and 1, 3, 6, 12, and 24 hours thereafter. No difference between the groups was found in bypass time, ECC flow or volume, or fluid balance. Significant differences in favor of Group I were found in pHb (p less than 0.05), beta-TG (p less than 0.01), D-D (p less than 0.05), and platelet counts (p less than 0.05). These differences were clearly ECC time dependent, became significant after 90 minutes of bypass, but disappeared within hours after surgery. No difference in patient outcome, ICU time, or need for volume substitution was seen. It is concluded that the RP can be safely used for routine ECC, but should be supplied with a CP in complex and prolonged cardiosurgical procedures to avoid severe postperfusion syndrome.