Cytopathic effects of Actinobacillus actinomycetemcomitans on monkey blood leukocytes

Taichman, Norton S.; Shenker, Bruce J.; Tsai, Chi‐Cheng; Glickman, Lawrence T.; Baehni, P; Stevens, R. H.; Hammond, Benjamin F.

doi:10.1111/j.1600-0765.1984.tb00802.x

Cited by 48 publications

(30 citation statements)

References 19 publications

(10 reference statements)

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“…2 RTX toxins are subdivided into two classes based upon their target cell specificity. A. actinomycetemcomitans leukotoxin kills a narrow range of target cell types including lymphoid cells and granulocytes from man and certain primates (38,39). The distribution pattern of CD11a-CD18 coincides with the range of cells susceptible to A. actinomycetemcomitans leukotoxin.…”

Section: Discussionmentioning

confidence: 94%

RTX Toxins Recognize a β2 Integrin on the Surface of Human Target Cells

Lally

Kieba

Satō

et al. 1997

Journal of Biological Chemistry

248

289

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Section: Discussionmentioning

confidence: 94%

RTX Toxins Recognize a β2 Integrin on the Surface of Human Target Cells

Lally

Kieba

Satō

et al. 1997

Journal of Biological Chemistry

248

289

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“…As previously mentioned, ␤ 2 -integrin is the membrane receptor that provides the selectivity by which LtxA targets leukocytes (14)(15)(16). Despite this, LtxA is able to lyse cells that do not express ␤ 2 integrin, such as erythrocytes, from various species (13,64).…”

Section: Discussionmentioning

confidence: 99%

“…Similar to HlyA, LtxA shows marked erythrotoxic effects via ATP release and subsequent P2X 1 and P2X 7 receptor activation (13). LtxA also belongs to the RTX family but is, in terms of cell lysis, more aggressive toward macrophages and leukocytes (14)(15)(16). Interestingly, the lysis of human monocytes involves activation of caspase 1 and release of interleukin-1␤ (IL-1␤) (17,18), which is closely associated with P2X 7 activation (for a review, see references 19 and 20).…”

mentioning

confidence: 99%

Inhibition of P2X Receptors Protects Human Monocytes against Damage by Leukotoxin from Aggregatibacter actinomycetemcomitans and α-Hemolysin from Escherichia coli

et al. 2016

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␣-Hemolysin (HlyA) from Escherichia coli and leukotoxin A (LtxA) from Aggregatibacter actinomycetemcomitans are important virulence factors in ascending urinary tract infections and aggressive periodontitis, respectively. The extracellular signaling molecule ATP is released immediately after insertion of the toxins into plasma membranes and, via P2X receptors, is essential for the erythrocyte damage inflicted by these toxins. Moreover, ATP signaling is required for the ensuing recognition and phagocytosis of damaged erythrocytes by the monocytic cell line THP-1. Here, we investigate how these toxins affect THP-1 monocyte function. We demonstrate that both toxins trigger early ATP release and a following increase in the intracellular receptors markedly reduces toxin-induced cytolysis. This pattern is paralleled in freshly isolated human monocytes from healthy volunteers. Interestingly, only a minor fraction of the toxin-damaged THP-1 monocytes eventually lyse. P2X 7 receptor inhibition generally prevents cell damage, except from a distinct cell shrinkage that prevails in response to the toxins. Moreover, we find that preexposure to HlyA preserves the capacity of THP-1 monocytes to phagocytose damaged erythrocytes and may induce readiness to discriminate between damaged and healthy erythrocytes. These findings suggest a new pharmacological target for protecting monocytes during exposure to poreforming cytolysins during infection or injury.␣ -Hemolysin (HlyA) is an important virulence factor frequently produced by strains of pathogenic Escherichia coli (1-3). The frequency with which HlyA-producing E. coli strains are isolated from patients increases with severity of the disease (for a review, see reference 2). HlyA is a pore-forming repeat in toxin (RTX) family member which inserts itself receptor independently into cell membranes (1). The cytotoxic effect of HlyA is massively amplified by ATP release, presumably through the HlyA pore (4) and following P2X receptor activation (5, 6). In erythrocytes, P2X 1 and P2X 7 receptors have been implicated in HlyA-induced hemolysis, and blocking of either of these receptors substantially reduces the hemolysis (5, 6). Interestingly, insertion of a HlyA pore does not cause immediate cell swelling and rupture but initially triggers a significant volume reduction that results from an increase in the intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) followed by activation of the Ca 2ϩ -sensitive K ϩ and Cl Ϫ channels K Ca 3.1 and TMEM16A (7). During erythrocyte shrinkage, cells expose phosphatidyl serine (PS) in the outer plasma membrane leaflet (7). Recently, we discovered that THP-1 monocytes are more likely to recognize and phagocytose erythrocytes that have been exposed to HlyA (8). This phagocytosis is prevented if HlyA-induced cell damage is diminished by P2X receptor antagonists or if cell shrinkage and PS exposure are blocked (8).Leukotoxin A (LtxA) is a virulence factor often released from Aggregatibacter actinomycetemcomitans in the periodontal connective tissue (9-11). ...

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“…Such microorganisms, for example A . actinomycetemcomitans, may produce cytopathic changes in the neutrophils by the release of toxins, which ultimately lead to the lysis of these cells [32][33][34].…”

mentioning

confidence: 99%