Vitronectin (S protein) augments the functional activity of monocyte receptors for IgG and complement C3b.

An arginine-glycine-aspartic acid sequence (RGD in the single letter code for amino acids) is present in the cell attachment site of both vitronectin and fibronectin. Inasmuch as fibronectin and synthetic peptides containing RGD enhance ingestion of opsonized particles by monocytes, we investigated the effects of vitronectin on phagocytosis by monocytes of sheep erythrocytes bearing IgG (EA) or complement C3b (EC3b). Peripheral blood monocytes were isolated by countercurrent elutriation and allowed to adhere to slides that had been coated with either vitronectin or fibronectin. Next, EA or EC3b were incubated with the adherent monocytes, and phagocytosis was subsequently quantified. Vitronectin caused the same dose dependent increase in phagocytosis as fibronectin. The augmentation of phagocytosis of EA induced by vitronectin could be inhibited by the F(ab')2 fragments of anti-vitronectin IgG but not by preimmune F(ab')2. The maximum phagocytosis of EA induced by vitronectin could not be enhanced by the addition of fibronectin, suggesting that vitronectin and fibronectin act on the same population of monocytes and that the two proteins stimulate the same mechanism through which the enhanced phagocytosis is mediated. Fibronectin and vitronectin caused a tenfold increase in the attachment of EC3b to monocytes, but phagocytosis was augmented minimally. These studies demonstrate that vitronectin modulates interactions between monocytes and opsonized particles.

Active tuberculosis in the medical intensive care unit: a 15-year retrospective analysis.

Of approximately 6000 admissions to the Henry Ford Hospital medical ICU between October 1969 and September 1984, 61 (1%) had active tuberculosis (TB). Forty-three (70%) of these 61 had acute respiratory failure (ARF). TB was considered to be the sole cause of ARF in 12 and contributory in 31. Eighteen patients with TB but without ARF were admitted for treatment of other critical illnesses. Alcoholism was present in 31 (51%) of the TB patients. Only one of 12 whose ARF was caused primarily by TB had a history of known TB at the time of admission. Important factors contributing to ARF in TB patients included Gram-negative pneumonia and/or sepsis, chronic obstructive pulmonary disease, prior TB with anti-TB medication noncompliance, and malignancy. Six patients were not suspected of having TB when admitted to the medical ICU; three patients who had not been treated for TB were found to have TB on autopsy. The inhospital mortality rate for all patients with TB requiring intensive care was 67%, but was 81% in those with ARF.

Flecanide-induced immune neutropenia. Documentation of a hapten-mediated mechanism of cell destruction.

Immune-mediated granulocytopenia due to cardiac antiarrhythmic medications is a rare, but potentially dangerous, event. This article characterizes the first case, to our knowledge, of severe granulocytopenia associated with the administration of flecanide acetate, a new class I antiarrhythmic drug. Immunologic studies determined that flecanide was capable of binding to the surface of normal neutrophils. The patient's serum contained an IgG antibody that could specifically bind to the haptenized neutrophils, presumably mediating enhanced destruction of mature granulocytes both in the serum and within the bone marrow. Cessation of flecanide therapy resulted in resolution of the granulocytopenia. The titer of antineutrophil antibody in the patient's serum decreased to background levels within the next five months. Similar antibodies were not found in serum from nonsensitized individuals. The capacity of flecanide to bind to normal neutrophils may prove to be a significant risk factor for the subsequent development of antineutrophil antibodies and agranulocytosis in patients receiving this drug. Careful hematologic monitoring of all patients who are receiving this medication is, therefore, strongly urged.