To summarize, it is possible that T cell activation in the plaque has four different effects: a direct inhibition of smooth muscle proliferation mediated by IFN-gamma, an indirect stimulation of smooth muscle proliferation via IFN-induced macrophage activation, an induction of responsiveness to PDGF by induction of PDGF receptor expression, and finally, an up-regulation of HDL receptors. The net effect of T cell activation during the vascular response to injury may, therefore, depend on the balance between these mechanisms in any given situation during lesion development. T cell activation may itself be regulated by apolipoprotein E-containing LDL, which thus could form a direct link between lipoprotein accumulation and immune activation. We have recently tried to assess the effect of T cell activation during the response to experimental arterial injury with the use of a drug model. Cyclosporin A is a drug that specifically inhibits T cell activation. Rats treated with cyclosporin A for a short period had significantly smaller intimal lesions than did controls after balloon injury. This could be due to an inhibition of T cell activation, resulting in an inhibition of monocyte-macrophage activation and thereby loss of an important stimulus for intimal cell proliferation. When interpreting these results, one must, however, bear in mind that cyclosporin A could exert as yet unknown nonimmune vascular effects. It is also worth stressing that cell proliferation in the human atherosclerotic plaque may not be as high as in experimental animal lesions. In fact, cell replication may be a very rare event in the average advanced atherosclerotic plaque. Cell proliferation may, however, be associated with an episodic growth of lesions, and growth factor-mediated responses could, therefore, be important for the eventual clinical outcome in the individual patient. In conclusion, cytokines produced during the immune response affect growth and differentiation of vascular cells and could modulate both the response to injury and the local lipid metabolism in an atherosclerotic plaque There is indirect support for paracrine secretion of several of these factors in the atherosclerotic plaque, and activated T lymphocytes and macrophages are abundant in the plaque. This points to the possibility that specific immune responses are associated with the development of atherosclerosis. It is unknown, however, to what extent such immune responses occur or which antigens may elicit these responses.

SummaryThe major characteristics of human atherosclerotic lesions are similar to those of a chronic inflammatory reaction, namely fibrosis, mesenchymal cell proliferation, the presence of resident macrophages, and cell necrosis. Atherosclerosis exhibits in addition the feature of lipid (mainly cholesterol) accumulation . The results ofthe present report demonstrate that a specific cholesterolcontaining lipid particle present in human atherosclerotic lesions activates the complement system to completion. Thus, lipid could represent a stimulatory factor for the inflammatory reaction, whose underlying mechanistic basis may be, at least in part, complement activation . The complement-activating lipid was purified from saline extracts of aortic atherosclerotic lesions by sucrose density gradient centrifugation followed by molecular sieve chromatography on Sepharose 2B. It contained little protein other than albumin, was 100-500 nm in size, exhibited an unesterified to total cholesterol ratio of 0.58 and an unesterified cholesterol to phospholipid ratio of 1.2. The lipid, termed lesion lipid complement (LCA), activated the alternative pathway ofcomplement in a dose-dependent manner. Lesion-extracted low density lipoprotein (LDL) obtained during the purification procedure failed to activate complement. Specific generation of C3a desArg and C5b-9 by LCA indicated C3/C5 convertase formation with activation proceeding to completion. Biochemical and electron microscopic evaluations revealed that much of the C5b-9 present in atherosclerotic lesions is membraneous, rather than fluid phase SC5b-9 . The observations reported herein establish a link between lipid insudation and inflammation in atherosclerotic lesions via the mechanism of complement activation. therosclerosis shares in common with chronic inflamma-1A tion the features ofleukocyte infiltration, fibrosis, mesenchymal cell proliferation, and tissue necrosis . Complement plays a central role in many inflammatory and immune diseases, and most of the complement components have now been identified in human atherosclerotic lesions (1) . Of particular importance is the presence of C5b-9 terminal complement complexes since their assembly indicates that complement activation with C3/C5 convertase formation has taken place. The respective convertases cleave C3 and C5 generating the anaphylatoxins C3a and C5a, which in turn mediate proinflammatory leukocyte functions (2) . The C5b-9 complex, in addition to its potential cytolytic effect, can influence cell physiology in sublytic doses via activation of various calcium-dependent pathways (3) .In a previous report, we demonstrated a temporal and spatial colocalization of C5b-9 complexes and lipid in the aortic tunica intima of cholesterol-fed rabbits (4) . Lipid vesicles rich in unesterified cholesterol are an early and consistent feature of human and animal atherosclerotic lesions (5-11) . In vitro, liposomes containing a >50 mole percent of unesterified cholesterol activate complement to completion (12, 13) . We therefore su...

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Chemotaxonomic and 16s ribosomal DNA sequence analyses of an isolate from the sputum of a patient with a mycobacterial lung infection clearly delineated a new species of the genus Tsukarnurella. This new species can be defined on the basis of genotypic and phenotypic data. The name Tsukamurella pulmonis sp. nov. is proposed for this organism; the type strain is IMMIB D-1321T (= DSM 44142T). This isolate shows 44.2 and 36.2% DNA relatedness to Tsukamurella paurometabola DSM 20162T (T = type strain) and Tsukamurella inchonensis DSM 44067T, respectively.

Terminal complement complexes arise as a final product of the complement activation sequence, and their assembly from native C5 through C9 proteins involves neoantigen formation, i.e., creation of unique antigenic epitopes not present on the native unassembled proteins. 89 Thus, immunological detection techniques utilizing antibodies to C5b-9 neoantigens reliably indicate that complement activation has taken place.Activation of complement is controlled at each step in the activation sequence. Eleven distinct proteins with complement regulatory activity have been described. 10Seven of the regulatory proteins are fluid-phase molecules and four are cell membrane glycoproteins. At present, the complement regulatory mechanisms operable in atherosclerotic lesions are unknown. Macrophages, a common component of lesions, possess cell surface complement regulatory molecules 11 -14 ; in addition, they are capa-