Phagocytosis by Polymorphonuclear Leucocytes from Patients with Renal Failure

Brogan, T. D.

doi:10.1136/bmj.3.5565.596

Cited by 37 publications

(19 citation statements)

References 4 publications

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“…This finding is in agreement with other reports demonstrating reduced phagocytosis in uremic patients [1][2][3][4][5]. Southwick and Stossel [29] showed wide variation in phagocytosis in normal sub jects.…”

Section: Discussionsupporting

confidence: 83%

“…Some investigators reported impaired phagocytosis with the defect residing in the PMNL [1,2], while others found that the serum of uremic patients contains an inhibitor of phagocytosis [3][4][5], In contrast, several stud ies could not confirm defective phagocytosis in CRF [6, affects random migration of these cells [12] as well as their degranulation [13]. It is theoretically possible that the high blood levels of PTH in CRF patients affect the phagocytic function of their PMNL.…”

Section: Introductionmentioning

confidence: 99%

“…Available data on the phagocytic function of the poly morphonuclear leukocytes (PMNL) in patients with chronic renal failure (CRF) are controversial [1][2][3][4][5][6][7]. Some investigators reported impaired phagocytosis with the defect residing in the PMNL [1,2], while others found that the serum of uremic patients contains an inhibitor of phagocytosis [3][4][5], In contrast, several stud ies could not confirm defective phagocytosis in CRF [6, affects random migration of these cells [12] as well as their degranulation [13].…”

Section: Introductionmentioning

confidence: 99%

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Impaired Phagocytosis in Dialysis Patients: Studies on Mechanisms

et al. 1991

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Dialysis patients have increased susceptibility to infection and this is, in part, due to impaired phagocytic and bactericidal activities of polymorphonuclear leukocytes (PMNL). The mechanisms responsible for the reduced phagocytosis are not known. Dialysis patients have elevated blood levels of parathyroid hormone (PTH), and available data indicate that PMNL is a target cell for PTH. Chronic exposure to excess PTH may cause accumulation of calcium in PMNL which in turn could adversely affect cellular events leading to their dysfunction. We studied phagocytosis, resting levels of cytosolic calcium ([Ca²⁺]_i), ATP content and the rise in [Ca²⁺]_i in response to ligation of Fcγ RIII receptors with 3G8 monoclonal antibody in PMNL from 37 dialysis patients and 48 normal subjects. The PMNL from the dialysis patients displayed impaired phagocytosis, elevated resting levels of [Ca²⁺]_i, decreased ATP content and a smaller rise in [Ca²⁺]_i in response to various doses of 3G8 monoclonal antibody as compared to values obtained in PMNL of normal subjects. Our results suggest that derangements in cellular metabolism and possibly an abnormality in Fcγ RIII interaction with antibody and/or the consequences of such interaction are responsible, at least in part, for the impaired phagocytosis of PMNL of dialysis patients. Our data are consistent with the notion that excess PTH may play an important role in the processes leading to impaired phagocytosis.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impaired Phagocytosis in Dialysis Patients: Studies on Mechanisms

et al. 1991

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“…Using phase-contrast microscopy, PMN from patients with renal failure have been shown to have more prominent cytoplasmic granules (45) and are reported to have increased intracellular cathepsin D (46). Already mentioned in this discussion, several intracellular substances released from granulocytes are known to inactivate CD chemotactic factors (26,29,30).…”

Section: Cia In Hd Patient Serummentioning

confidence: 99%

Serum Inhibitor of C5 Fragment-Mediated Polymorphonuclear Leukocyte Chemotaxis Associated with Chronic Hemodialysis

Goldblum¹,

Epps²,

Reed³

1979

J. Clin. Invest.

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A B S T R A C T Abnormal granulocyte chemotaxis has been described in chronic hemodialysis patients. In this study, sera from 53 hemodialysis patients were tested for chemotactic inhibitory activity by a modified Boyden technique. Chemotactic inhibitory activity, defined as >20% inhibition of normal granulocyte chemotaxis, was found in 45% of patients. Only sera from patients having undergone >3 mo hemodialysis displayed chemotactic inhibitory activity and retained this inhibitory activity when retested 9 mo later. Four of five patients who had initially undergone <3 mo hemodialysis and lacked serum chemotactic inhibitory activity developed inhibitory activity when tested 9 mo later. Clinical evaluation ofpatients with serum chemotactic inhibitory activity showed that these patients did not have a significantly increased incidence of infection, although a trend toward decreased mortality during the time of study was observed (P = 0.0721).Serum chemotactic inhibitory activity was heat stable at 56°C for 30 min and concentration dependent. The major inhibitory component was found to have a sedimentation coefficient of 4S by sucrose density gradient centrifugation. The chemotactic inhibitory activity was not precipitated by 30% ammonium sulfate, but was partially precipitated by 50% ammonium sulfate.Inhibitory sera effectively suppressed neutrophil migration in response to chemotactic C5 fragment and Escherichia coli derived chemotactic factor but was least effective in a system mediated by casein. Furthermore, normal neutrophils preincubated in hemodialysis patient sera displayed normal chemotactic responsiveness indicating a lack ofcell-directed inhibition. Serum fractions that contained the inhibitor were found to

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“…Defective leukocyte function manifested by impaired migration [1,2] and reduced phagocytic [3][4][5] and bacte ricidal activity [6] has been observed in patients with ure mia. Also, sera from dialysis patients contain a heat-stable factor that inhibited granulocyte chemotaxis [7], The mechanisms and/or the potential uremic factors underly ing these defects in leukocyte functions are not known.…”

Section: Introductionmentioning

confidence: 99%

Effect of Parathyroid Hormone on Random Migration of Human Polymorphonuclear Leukocytes

Doherty¹,

LaBelle²,

Collins³

et al. 1988

Am J Nephrol

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Derangements in leukocyte function occur in patients with primary hyperparathyroidism and in those with uremia, which is a state of secondary hyperparathyroidism, suggesting that parathyroid hormone (PTH) may affect leukocyte function. We examined the interaction between PTH and random migration of human polymorphonuclear leukocytes (PMNL) utilizing a modified Boyden chamber. Intact 1–84 PTH but not its amino-terminal (1–34 PTH) or its carboxy-terminal (53–84 PTH) fragments produced marked and significant (p < 0.01) stimulation of random migration in a dose-dependent manner. Inactivation of 1–84 PTH abolished its effect and other peptide hormones (calcitonin, glucagon, insulin and vasopressin) did not stimulate migration of PMNL. The effect of PTH on migration was not due to action of the hormone on chemotaxis. PTH did not enhance cAMP or cGMP production by PMNL. The stimulation of PMNL motility by PTH was independent of calcium concentration in media, was not mimicked by calcium ionophore and was not blocked by verapamil. Quinidine also produced significant (p < 0.01) increase in random migration of PMNL and this effect was not additive to that of PTH. Prolonged exposure to PTH (16–20 h) was associated with significant inhibition of random migration of PMNL. The migration of PMNL from patients with advanced renal failure was significantly (p < 0.01) reduced and there was a significant (p < 0.01) inverse relationship between random migration of PMNL and serum levels of PTH. Also PTH produced only modest stimulation of random migration of PMNL in most patients with renal failure. The data show that (1) PMNL are target cells for intact 1–84 PTH; (2) the effect of PTH on PMNL migration is specific to the hormone and is related to its biological activity; (3) this action of the hormone is not mediated by calcium influx into PMNL nor by stimulation of cAMP or cGMP production in these cells but may be due to redistribution of cytosolic calcium between various cell organelles; (4) prolonged exposure to intact PTH may adversely affect random migration of PMNL, and (5) the migration of PMNL is impaired in most patients with chronic renal failure and it is inversely related to serum levels of PTH. The data are consistent with the notion that the state of secondary hyperparathyroidism of chronic renal failure is responsible for altered PMNL migration and assign a new dimension for PTH toxicity in these patients.

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Phagocytosis by Polymorphonuclear Leucocytes from Patients with Renal Failure

Cited by 37 publications

References 4 publications

Impaired Phagocytosis in Dialysis Patients: Studies on Mechanisms

Impaired Phagocytosis in Dialysis Patients: Studies on Mechanisms

Serum Inhibitor of C5 Fragment-Mediated Polymorphonuclear Leukocyte Chemotaxis Associated with Chronic Hemodialysis

Effect of Parathyroid Hormone on Random Migration of Human Polymorphonuclear Leukocytes

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