A continuous, spectroscopic analysis of the kinetics of elastase secretion by neutrophils. The dependence of secretion upon receptor occupancy.

Sklar, Larry A.; McNeil, V.M.; Jesaitis, Algirdas J.; Painter, Richard G.; Cochrane, Charles G.

doi:10.1016/s0021-9258(19)83801-2

Cited by 103 publications

(16 citation statements)

References 17 publications

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“…Compared with the response to opsonized zymosan or hyphae, detectable actin polymerization stimulated by unopsonized hyphae was delayed, occurring subsequent to attachment and spreading and without a direct relationship to the release of granule markers. The time course of actin polymerization (but not degranulation) resembled that of other previously defined delayed responses to unopsonized hyphae (28,29,31), including increases in putative second messengers related to the genesis of the neutrophil respiratory burst (21,22,40,41,43,54), i.e., cytosolic calcium (42) and 1P3 (1,6). These data raise the possibility that neutrophil superoxide generation and degranulation responses to particulate stimuli such as microorganisms may be initiated by different mechanisms.…”

supporting

confidence: 67%

Stimulation of neutrophil actin polymerization and degranulation by opsonized and unopsonized Candida albicans hyphae and zymosan

Kolotila

Diamond

1988

Infect Immun

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We previously showed that unopsonized Candida albicans hyphae stimulated a delayed rise in the putative neutrophil second messengers Ca2+ and inositol 1,4,5-trisphosphate and subsequent O2- release, as compared with opsonized hyphae or zymosan. Therefore, cytoskeletal and degranulation temporal responses to these stimuli were examined. Unopsonized zymosan elicited no neutrophil responses under the experimental condition used. Neutrophil actin polymerization (quantitated by fluorescent measurements of NBD phallacidin) was rapid after stimulation by opsonized hyphae or zymosan (peaking at 1 and 2 min, respectively). This corresponded to observed changes in microscopic actin polymerization, measured with rhodamine phalloidin, which progressed from initially diffuse to collarlike to cylinderlike staining patterns surrounding the hyphae. Compared with opsonized hyphae, unopsonized hyphae resulted in a delayed appearance of the last two visible patterns (P less than 0.05) and in quantitative actin polymerization despite similarly rapid initial contact and spreading over the hyphae by neutrophils. Unlike other neutrophil responses, degranulation did not follow the delayed patterns of responses to stimulation with unopsonized hyphae. In the absence of the release of the cytoplasmic marker lactate dehydrogenase, the release of beta-glucuronidase, an azurophil granule marker, gradually and progressively rose in response to all of the stimuli but unopsonized zymosan. The low but significant levels observed were within a range consistent with published results for degranulation responses to particulate stimuli without cytochalasin B. A quantitative immunoassay of lactoferrin, a specific granule marker, detected no release into supernatants, and immunofluorescent staining indicated concomitant depletion of lactoferrin from neutrophil granules and binding to hyphal and neutrophil surfaces after stimulation by unopsonized hyphae. Thus, the delayed actin polymerization response to unopsonized hyphae occurred subsequent to neutrophil attachment and spreading and resembled the temporal sequence of other neutrophil responses linked to the respiratory burst. In contrast, the degranulation responses to all stimuli appeared to begin and progress gradually after observed attachment and spreading of the neutrophil over hyphal surfaces without a clear temporal relationship to rises in cytoplasmic Ca2+ or F-actin. In addition, the avid binding of released lactoferrin to cell surfaces eliminates its value as a quantitative marker of enzyme release but raises the possibility that it might participate in fungicidal activity.(ABSTRACT TRUNCATED AT 400 WORDS)

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supporting

confidence: 67%

Stimulation of neutrophil actin polymerization and degranulation by opsonized and unopsonized Candida albicans hyphae and zymosan

Kolotila

Diamond

1988

Infect Immun

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“…It is probable, moreover, that the anomalies in chemotactic response are related to the anomaly in binding. The lack of any corresponding anomalies in the degranulation response is presumably related to the different nature of this response, most likely to its rapidity [45,46] compared with the prolonged time course of the chemotactic response [47,48]. Although the latter response requires receptor recycling [49,50], it is unlikely, in view of the differences in binding patterns in the absence of recycling (at 4 °C), that the anomalies in this response are due solely to anomalous recycling of receptors occupied by the potent analogues.…”

Section: Discussionmentioning

confidence: 99%

The significance of functional receptor heterogeneity in the biological responses of the rabbit neutrophil to stimulation by chemotactic formyl peptides

Kermode

Freer

Becker

1991

Biochemical Journal

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The characteristics of binding to the chemotactic receptors on rabbit peritoneal neutrophils were examined for seven formyl peptide analogues. These receptor-binding characteristics were compared with the abilities of the analogues to induce the biological responses of degranulation and chemotaxis. Five of the analogues showed distinct functional heterogeneity in their receptor-binding patterns, whereas the two most potent compounds displayed homogeneous binding patterns. The relative potencies of the formyl peptide analogues for stimulation of degranulation correlated well with their relative potencies for high-affinity, but not low-affinity, binding. The biphasic patterns for stimulation of chemotactic migration were similar for the less potent analogues, and their potencies paralleled those for both degranulation and receptor binding. In contrast, the most potent analogues induced a greater maximal extent of chemotactic migration than the other compounds, but displayed a lower than expected potency (i.e. they required higher than expected concentrations). These anomalies in the patterns of the chemotactic response cannot be reconciled with a simple receptor model comprising two independent classes of receptors. Instead, a model comprising interconvertible states of different affinities is proposed. The state of higher affinity appears to play a central role in initiation of both degranulation and chemotaxis. The more potent formyl peptide analogues are thought to stabilize an activated, higher-affinity, state of the receptor; this can explain their greater efficacy in stimulating chemotaxis. The proposed model may also be applicable to other receptors that are coupled by a guanine-nucleotide-binding regulatory protein to their associated effector.

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“…Azurophilic degranulation was determined on the basis of NE release from human neutrophils, as reported previously (Sklar et al, 1982 ). In brief, human neutrophils (6 × 10 5 cells·ml −1 ) were incubated with DMSO or bletinib after treatment with 1 mM CaCl 2 and 100 μM NE substrate (methoxysuccinyl‐Ala‐Ala‐Pro‐Val‐ p ‐nitroanilide) at 37°C for 5 min.…”

Section: Methodsmentioning

confidence: 99%

Bletinib ameliorates neutrophilic inflammation and lung injury by inhibiting Src family kinase phosphorylation and activity

Kao

Chen

Wang

et al. 2021

British J Pharmacology

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A continuous, spectroscopic analysis of the kinetics of elastase secretion by neutrophils. The dependence of secretion upon receptor occupancy.

Cited by 103 publications

References 17 publications

Stimulation of neutrophil actin polymerization and degranulation by opsonized and unopsonized Candida albicans hyphae and zymosan

Stimulation of neutrophil actin polymerization and degranulation by opsonized and unopsonized Candida albicans hyphae and zymosan

The significance of functional receptor heterogeneity in the biological responses of the rabbit neutrophil to stimulation by chemotactic formyl peptides

Bletinib ameliorates neutrophilic inflammation and lung injury by inhibiting Src family kinase phosphorylation and activity

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