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Mammalian plasma membranes, including the myocardial sarcolemma, are abundantly glycosylated. Sialic acid is a ubiquitous anionic sugar found at the periphery of sarcolemmal glycoconjugates. The physiological role of this sugar is not clear, but neuraminidase, which specifically hydrolyzes sialic acid from the sarcolemma, has been found to increase calcium exchange, cause electrophysiological abnormalities, and enhance the transient (T) calcium current in cardiac myocytes. The purpose of this study was to better characterize the effect of neuraminidase on cellular calcium (Ca) and contractile function. Neuraminidase removed up to 57% of total sialic acid from the cells. 45Ca exchange was measured and neuraminidase was found to increase cell calcium proportional to the amount of sialic acid removed (18.6 +/- 0.8 mmol/kg dry w, maximally). Over 80% of the increment in calcium remained rapidly exchangeable (t1/2 less than 15 s) under non-perfusion limited conditions and was inhibited by cations (La greater than Cd greater than Mn greater than Mg) and nifedipine. Using a video-monitoring system, neuraminidase was observed to transiently increase cell shortening during contraction (30 +/- 9%), with progression to arrhythmias followed by cessation of contraction. These results indicate that neuraminidase, probably by removing sarcolemmal sialic acid residues, greatly augments cellular calcium in cultured cardiac myocytes. Most of the increment in Ca induced by neuraminidase was very rapidly exchangeable and most likely mediated by a Ca specific mechanism. Additionally, neuraminidase treatment altered contractile function in a manner consistent with elevated cellular Ca. Despite the many-fold increase in cellular Ca induced by sialic acid removal, cells recovered and demonstrated rhythmic contractions upon return to control incubation conditions.

The pathogenesis of pulmonary edema that occurs during interleukin-2 therapy has often been attributed to an increase in pulmonary capillary permeability. However, renal insufficiency, fluid overload, and hypotension also develop in many patients. These manifestations of systemic toxicity may contribute to the development of pulmonary edema during therapy. Understanding the cause of pulmonary edema during interleukin-2 therapy could directly affect patients' care. Therefore, we reviewed the chest radiographs and clinical course of 54 patients who received high-dose interleukin-2 therapy and lymphokine-activated killer cells for advanced carcinoma. The type, frequency, and course over time of pulmonary abnormalities were recorded and correlated with clinical measures of renal function, fluid status, and blood pressure. Focal or diffuse parenchymal lung opacities were found on radiographs in 43 (80%) of 54 patients. Findings of interstitial pulmonary edema were most common, occurring in 76% of patients. Weight gain, hypotension, and elevation of the serum creatinine level were not associated statistically with interstitial edema. Diffuse air-space disease developed in 20% of patients. Focal consolidation, which was associated with positive central venous catheter cultures (p less than .03), developed in 28% of patients. Pleural effusion occurred in 48% of patients and was associated with all types of parenchymal disease. These data suggest that the frequent development of pulmonary edema during interleukin-2 therapy is not due to renal insufficiency, fluid overload, or hypotension, but is more likely the result of an interleukin-2-related increase in pulmonary capillary permeability.