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Published on: June 23, 2013
The actin-binding protein, lymphocyte-specific protein 1, is expressed in human leukocytes and human myeloid and
1Department of Pediatrics, University of Alabama School of Medicine, Birmingham 35233, USA.
Insights
Lymphocyte-specific protein 1 (LSP1) is present in all human leukocytes and its expression increases during myeloid cell differentiation. This actin-binding protein may regulate leukocyte cytoskeleton and motility, prompting a name change to leufactin.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Lymphocyte-specific protein 1 (LSP1) was initially identified as a lymphocyte-specific actin-binding protein.
- LSP1 was later found to be overexpressed in polymorphonuclear neutrophils (PMN) associated with neutrophil actin dysfunction (NAD 47/89).
- This suggests a potentially significant regulatory role for LSP1 expression in myeloid cells.
Purpose of the Study:
- To analyze the expression of LSP1 in various human leukocytes and myeloid cell lines.
- To investigate the regulation of LSP1 expression during granulocytic and monocytic differentiation.
- To evaluate the potential role of LSP1 in leukocyte cytoskeleton and motility.
Main Methods:
- Northern blot analysis to detect LSP1 mRNA.
- Immunoblotting to detect LSP1 protein levels.
- Analysis of LSP1 expression in uninduced and differentiated myeloid cell lines (PLB985, HL60, U937) and lymphoid cell lines.
Main Results:
- LSP1 is expressed in all human leukocytes, including PMN, lymphocytes, and monocytes, with varying levels.
- LSP1 expression is minimal in uninduced myeloid cell lines but significantly up-regulated during granulocytic and monocytic differentiation.
- In HL60 cells, LSP1 mRNA and protein increased up to eightfold during granulocytic differentiation and four- to fivefold during monocytic differentiation.
Conclusions:
- LSP1 is not lymphocyte-specific and is expressed in all human leukocytes.
- LSP1 expression is dynamically regulated during myeloid cell differentiation.
- Given its F-actin binding properties and widespread expression, LSP1 likely plays a crucial role in regulating the microfilamentous cytoskeleton and motility of all leukocytes. A name change to leufactin is proposed.
Abstract:
Lymphocyte-specific protein 1 (LSP1) was originally reported as a lymphocyte-specific actin-binding protein using murine LSP1 probes. Subsequently, we identified LSP1 in polymorphonuclear neutrophils (PMN) and showed that it is the overexpressed 47-kDa protein in neutrophil actin dysfunction with 47- and 89-kDa abnormalities. This suggests that regulation of LSP1 expression in myeloid cells may be a functionally important event. LSP1 expression in human leukocytes, lymphoid cell lines, and myeloid cell lines (PLB985, HL60, and U937), uninduced (U) or induced to granulocytic (GI) or monocytic (MI) differentiation, was analyzed by Northern blot and immunoblot. By immunoblot, LSP1 is strongly expressed in PMN, less expressed in lymphocytes and monocytes (30-40% and 55-65% of the PMN level, respectively). By immunoblot and Northern blot, LSP1 is minimally expressed in U-PLB985 and U-HL60 (< 10% of the PMN level) and is weakly expressed in the B lymphoid cell line Daudi, but is not expressed in the pro-B, pre-B, T lymphoid cell lines tested, U-U937 or MI-U937. LSP1 mRNA and protein are up-regulated in GI-PLB985, GI-HL60, and MI-HL60. In HL60, LSP1 mRNA and protein increase in parallel to a maximum of eightfold the basal level on days 5 to 6 of granulocytic differentiation and four- to fivefold the basal level on day 3 of monocytic differentiation. The results show that LSP1 is expressed in all human leukocytes, and its expression is up-regulated during granulocytic and monocytic differentiation of myeloid cells in vitro. Since its overexpression is implicated in the functional pathogenesis of a novel human neutrophil motile dysfunction and microfilamentous cytoskeletal abnormality (NAD 47/89), finding LSP1 in all human leukocytes suggests that it plays a role in regulating microfilamentous cytoskeleton structure and motile function in all leukocytes. Since the protein is not lymphocyte specific and is an F-actin binding protein, and its isoforms are expressed in stromal and embryonic mesenchymal cells, we propose that the protein's name be changed to leufactin, as an abbreviated form of leukocyte F-actin binding protein.
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