Thromboxane A2 Mediates Augmented Polymorphonuclear Leukocyte Adhesiveness

Spagnuolo, Philip J.; Ellner, Jerrold J.; Hassid, Aviv; Dünn, Michael J.

doi:10.1172/jci109870

Cited by 191 publications

(45 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast, granulocyte depletion with hydroxyurea did not signif- icantly affect the E. coli endotoxin-induced pulmonary hypertension (7,9) although the endotoxin-induced pulmonary hypertension was attenuated after granulocyte depletion with nitrogen mustard (1 5). In vivo and in vitro experiments have shown that granulocytes are capable of synthesis of vasoactive substances after endotoxin stimulation (8,11). Granulocyte depletion should, therefore, reduce the source for these vasoactive metabolites, thereby explaining the reduction in pulmonary hypertension found in our study.…”

Section: Discussionmentioning

confidence: 56%

The Role of Granulocytes in the Pulmonary Response to Group B Streptococcal Toxin in Young Lambs

et al. 1987

View full text Add to dashboard Cite

ABSTRACT. Marked leukopenia and sequestration of granulocytes in the lung are consistently seen in severe early onset group B streptococcal (GBS) disease in human infants. To investigate the role of granulocytes as potential mediators in the pulmonary pathophysiology of this disease, the effects of intravenously administered GBS type 111 toxin were studied in young lambs before and after granulocyte depletion with hydroxyurea. Granulocyte depletion markedly reduced the 4-fold increase in total lung resistance and the decrease in dynamic compliance observed after GBS toxin. Granulocyte depletion significantly attenuated the pulmonary hypertension, hypoxemia and increased minute ventilation present during the first phase of the response (0.5-1 h after GBS toxin). It did not significantly alter the increase in body temperature, the marked increase in lung lymph thromboxane BZ concentrations during the first phase or the increase in lung lymph flow and protein clearance during the second phase of the response (3.5-5 h after GBS toxin). The results indicate that granulocytes are involved as mediators of the changes in lung mechanics seen after GBS toxin infusion in young lambs. Granulocytes contribute to the pulmonary hypertension and decrease in arterial oxygenation, but other mediators appear to be responsible for the injury of the vascular endothelium. (Pediatr Res 21: 159-165, 1987) Abbreviations Cdyn, dynamic compliance GBS, group B streptococcus LIP, lymph/plasma protein ratio P,,, pulmonary artery pressure RIA, resistance to air flow across the lungs TXB2, thromboxane B2 TGV, thoracic gas volume VT, tidal volume Vmi., minute ventilation P,,, pleural pressure V, flow Pa,, airway opening pressure P,,, transpulmonary pressure SG,, specific conductance f, frequency

show abstract

Section: Discussionmentioning

confidence: 56%

The Role of Granulocytes in the Pulmonary Response to Group B Streptococcal Toxin in Young Lambs

et al. 1987

View full text Add to dashboard Cite

show abstract

“…The importance of sequestered neutrophils in the microvascular dysfunction of the ex vivo perfused lung model was initially suggested by Seibert et al (24) in 1993 in a study in which neutrophils sequestered within the perfused lung were found to contribute significantly to the enhanced permeability associated with pulmonary ischemia-reperfusion injury. One may postulate that in the present study perfusion of the lung with U-46619 [and perhaps PGF 2␣ and PGI 2 (13,17,33,40)] may have acted on sequestered neutrophils, resulting in the generation of a respiratory burst and, ultimately, a neutrophil-mediated microvascular dysfunction (18,26). Other more recent studies have suggested that U-46619, as well as PGE 2 , PGF 2␣ , and PGI 2 , inhibits neutrophil activation, at least as manifested by increases in intracellular free calcium, leukoaggregation, and the release of superoxide radical, ␤-glucuronidase, and leukotriene B 4 (22,32,36).…”

Section: Discussionmentioning

confidence: 93%

Prostaglandins potentiate U-46619-induced pulmonary microvascular dysfunction

Wright¹,

Kim²,

Rogers

et al. 2000

Journal of Applied Physiology

View full text Add to dashboard Cite

.-The induction of cyclooxygenase is an important event in the pathophysiology of acute lung injury. The purpose of this study was to examine the synergistic effects of various cyclooxygenase products (PGE 2 , PGI 2 , PGF 2␣ ) on thromboxane A 2 (TxA 2 )-mediated pulmonary microvascular dysfunction. The lungs of SpragueDawley rats were perfused ex vivo with Krebs-Henseleit buffer containing indomethacin and PGE 2 (5 ϫ 10 Ϫ8 to 1 ϫ 10 Ϫ7 M), PGF 2␣ (7 ϫ 10 Ϫ9 to 5 ϫ 10 Ϫ6 M), or PGI 2 (5 ϫ 10 Ϫ8 to 2 ϫ 10 Ϫ5 M). The TxA 2 -receptor agonist U-46619 (7 ϫ 10 Ϫ8 M) was then added to the perfusate, and then the capillary filtration coefficient (K f ), pulmonary arterial pressure (Ppa), and total pulmonary vascular resistance (RT) were determined. The K f of lungs perfused with U-46619 was twice that of lungs perfused with buffer alone (P ϭ 0.05). The presence of PGE 2 , PGF 2␣ , and PGI 2 within the perfusate of lungs exposed to U-46619 caused 118, 65, and 68% increases in K f , respectively, over that of lungs perfused with U-46619 alone (P Ͻ 0.03). The RT of lungs perfused with PGE 2 ϩ U-46619 was ϳ30% greater than that of lungs exposed to either U-46619 (P Ͻ 0.02) or PGE 2 (P Ͻ 0.01) alone. When paired measurements of RT taken before and then 15 min after the addition of U-46619 were compared, PGI 2 was found to attenuate U-46619-induced increases in RT (P Ͻ 0.01). These data suggest that PGE 2 , PGI 2 , and PGF 2␣ potentiate the effects of TxA 2 -receptor activation on pulmonary microvascular permeability.capillary filtration coefficient; pulmonary vascular resistance; isolated perfused lung model THROMBOXANE A 2 (TxA 2 ) has been incriminated as an important mediator of the pulmonary microvascular dysfunction that characterizes tissue ischemia and reperfusion injury (29), endotoxin exposure (9), and cutaneous thermal injury (14). In these conditions, as well as others, TxA 2 has been shown to cause vasoconstriction and enhanced microvascular permeability. Upregulation of cyclooxygenase is an important event in the generation of TxA 2 during acute inflammatory states. Cyclooxygenase catalyzes the incorporation of molecular oxygen into arachidonic acid, yielding a cyclic endoperoxide (PGG 2 ); subsequent peroxidation yields PGH 2 , the precursor for the synthesis of TxA 2 and PGE 2 , PGI 2 , and PGF 2␣ . In general, each of these cyclooxygenase products is released by the lung in response to a particular inflammatory stimulus, albeit in varying amounts (9,14).Despite their common origin, the physiological effects of these substances on the pulmonary microvasculature are diverse. For example, TxA 2 and PGF 2␣ are constrictors of the pulmonary vasculature in rats, whereas PGI 2 is a potent vasodilator (4, 5). Furthermore, TxA 2 profoundly increases microvascular permeability, whereas the other agents have little, if any, effect by themselves (20, 27). Several investigators have reported that PGE 2 and PGI 2 potentiate the effects of histamine, bradykinin, and interleukin-1 on microvascular permeability (2,34,35). Thi...

show abstract

“…Leukotriene B 4 is a chemokinetic and aggregating substance released from activated neutrophils [8,15,36]. Stimulated neutrophils also produce thromboxane A 2, which enhances the aggregation and adhesiveness of the cells to nylon wool [17]. The production of these aggregating and adherence-increasing agents could result in diminished chemotaxis towards zymosan-activated serum and a decreased phagocytic capacity of polymorphonuclear leukocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Leukotriene B 4 [15], several monohydroxyeicosatetraenoic acids [16] and prostaglandin E 1 [6] are 0304-4165/84/$03.00 © 1984 Elsevier Science Publishers B.V. chemotactic for neutrophils. Arachidonic acid metabolites may play a role in the process of aggregation and adhesiveness of neutrophils [15,17]. Also, arachidonic acid itself affects the function of phagocytic cells.…”

Section: Introductionmentioning

confidence: 99%

Differences in the effect of arachidonic acid on polymorphonuclear and mononuclear leukocyte function

Nijkamp¹,

Henricks²,

Tol³

et al. 1984

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

Incubation of human polymorphonuclear leukocytes with arachidonic acid resulted in a stimulation of the oxidative metabolism of the cells. Upon stimulation with 80 #M arachidonic acid, neutrophils (5.106 cells/ml) produced superoxide (53 + 8 nmol/5.106 cells per 15 rain), generated chemiluminescence (1211 100 + 157000 cpm) and consumed oxygen (20 + 1 nmol/106 cells per 5 rain). The stimulation of the cell metabolism could be reduced 40-60% by prior incubation of the cells with 10 /xM indomethacin. Incubating polymorphonuclear leukocytes with arachidonic acid also resulted in a diminished chemotaxis towards an attractant, a decreased uptake of opsonized staphylococci and aggregation of the cells. This may be due to inhibitory products of arachidonic acid metabolism and toxic oxygen species produced during stimulated oxidative metabolism. The effects of arachidonic acid are specific for neutrophils, as mononuclear phagocytes only produced 17 + 8 nmol superoxide/5 • 106 cells per 15 min and generated 27000 + 15000 cpm chemiluminescence when stimulated with 80 /~M arachidonic acid. When monocytes and neutrophils were stimulated with particles such as opsonized staphylococci, the amount of superoxide produced, oxygen consumed and chemiluminescence generated were similar. The phagocytic activity of the monocytes was also not affected by prior incubation with arachidonic acid. We conclude that in contrast to monocytes, neutrophil metabolism can be stimulated with arachidonic acid and this stimulation resulted in a decreased phagocytic activity of these cells.

show abstract

Thromboxane A2 Mediates Augmented Polymorphonuclear Leukocyte Adhesiveness

Cited by 191 publications

References 32 publications

The Role of Granulocytes in the Pulmonary Response to Group B Streptococcal Toxin in Young Lambs

The Role of Granulocytes in the Pulmonary Response to Group B Streptococcal Toxin in Young Lambs

Prostaglandins potentiate U-46619-induced pulmonary microvascular dysfunction

Differences in the effect of arachidonic acid on polymorphonuclear and mononuclear leukocyte function

Contact Info

Product

Resources

About